RESUMO

RATIONALE: Although the mesocorticolimbic dopamine (DA) system is the main neurochemical substrate that regulates the addictive and reinforcing effects of ethanol (EtOH), other neurotransmitter systems, such as the acetylcholine (Ach) system, modulate DAergic function in the nucleus accumbens (nAcc). Previously, we reported that intra-nAcc administration of the nicotinic Ach receptor agonist cytisine increased oral EtOH self-administration. GABAB receptors in the nAcc are expressed in DAergic terminals, inhibit the regulation of DA release into the nAcc, and could modulate the effects of cytisine on oral EtOH self-administration. The present study assessed the effects of intra-nAcc administration of the GABAB receptor agonist baclofen (BCF) on the impacts of cytisine on oral EtOH self-administration. METHODS: Male Wistar rats were deprived of water for 23.30 h and then trained to press a lever to receive EtOH on an FR3 schedule until a stable response rate of 80 % was achieved. After this training, the rats received an intra-nAcc injection of the nAch receptor agonist cytisine, BCF, and cytisine or 2-hydroxysaclofen, BCF, and cytisine before they were given access to EtOH on an FR3 schedule. RESULTS: Intra-nAcc injections of cytisine increased oral EtOH self-administration; this effect was reduced by BCF, and 2-hydroxysaclofen blocked the effects of BCF. CONCLUSIONS: These findings suggest that the reinforcing effects of EtOH are modulated not only by the DA system but also by other neurotransmitter systems involved in regulating DA release from DAergic terminals.

Assuntos

Alcaloides , Azocinas , Baclofeno , Condicionamento Operante , Etanol , Agonistas dos Receptores de GABA-B , Agonistas Nicotínicos , Núcleo Accumbens , Quinolizinas , Ratos Wistar , Autoadministração , Animais , Masculino , Baclofeno/farmacologia , Baclofeno/administração & dosagem , Ratos , Alcaloides/farmacologia , Alcaloides/administração & dosagem , Azocinas/farmacologia , Azocinas/administração & dosagem , Quinolizinas/farmacologia , Quinolizinas/administração & dosagem , Agonistas dos Receptores de GABA-B/farmacologia , Agonistas dos Receptores de GABA-B/administração & dosagem , Núcleo Accumbens/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Etanol/administração & dosagem , Etanol/farmacologia , Condicionamento Operante/efeitos dos fármacos , Agonistas Nicotínicos/farmacologia , Agonistas Nicotínicos/administração & dosagem , Administração Oral , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Consumo de Bebidas Alcoólicas/psicologia , Alcaloides Quinolizidínicos

RESUMO

Alcohol use disorder (AUD) remains a critical public health issue worldwide, characterized by high relapse rates often triggered by contextual cues. This research investigates the neural mechanisms behind context-induced reinstatement of alcohol-seeking behavior, focusing on the nucleus accumbens and its interactions with the prelimbic cortex, employing Male Long-Evans rats in an ABA renewal model. In our experimental setup, rats were trained to self-administer 10 % ethanol in Context A, followed by extinction of lever pressing in the presence of discrete cues in Context B. The context-induced reinstatement of ethanol-seeking was then assessed by re-exposing rats to Context A or B under extinction conditions, aiming to simulate the environmental cues' influence on relapse behaviors. Three experiments were conducted: Experiment 1 utilized Fos-immunohistochemistry to examine neuronal activation in the nucleus accumbens; Experiment 2 applied the baclofen + muscimol inactivation technique to probe the functional importance of the nucleus accumbens core; Experiment 3 used Fos-immunofluorescence along with Retrobeads injection to investigate activation of neurons projecting from the prelimbic cortex to the nucleus accumbens core. Our findings revealed significant increases in Fos-immunoreactive nuclei within the nucleus accumbens core and shell during the reinstatement phase in Context A, underscoring the environment's potent effect on ethanol-seeking behavior. Additionally, inactivation of the nucleus accumbens core markedly reduced reinstatement, and there was a notable activation of neurons from the prelimbic cortex to the nucleus accumbens core in the ethanol-associated context. These results highlight the critical role of the nucleus accumbens core and its corticostriatal projections in the neural circuitry underlying context-driven ethanol seeking.

Assuntos

Comportamento de Procura de Droga , Etanol , Extinção Psicológica , Núcleo Accumbens , Ratos Long-Evans , Animais , Núcleo Accumbens/efeitos dos fármacos , Masculino , Etanol/administração & dosagem , Etanol/farmacologia , Comportamento de Procura de Droga/fisiologia , Ratos , Extinção Psicológica/fisiologia , Extinção Psicológica/efeitos dos fármacos , Autoadministração , Vias Neurais/fisiologia , Alcoolismo , Sinais (Psicologia) , Córtex Pré-Frontal/fisiologia , Córtex Pré-Frontal/efeitos dos fármacos , Baclofeno/farmacologia , Proteínas Proto-Oncogênicas c-fos/metabolismo , Muscimol/farmacologia

RESUMO

Oxytocin (OXT), a pro-social peptide, is increasingly recognized as a potential protective substance against drug addiction. In the context of ethanol, previous research has shown OXT's properties in reducing self-administration, alleviating motor impairment in rodents, and reducing craving in humans. However, its role in behavioral sensitization, a neuroadaptive response resulting from repeated drug exposure linked to an increased drug incentive, remains unexplored. OXT is recognized for its role in regulating the hypothalamic-pituitary-adrenal (HPA) axis, in which corticosterone is acknowledged as a significant factor in the development of behavioral sensitization. This study aimed to investigate the effects of carbetocin (CBT), an analogue of OXT, on the expression of behavioral sensitization to ethanol and the concurrent alterations in plasma corticosterone levels in male and female Swiss mice. We also aimed to confirm previous studies on OXT's impact on ethanol consumption in male mice, but with a focus on CBT, using the two-bottle choice model and the drinking in the dark (DID) methodology. For the sensitization study, the mice received either ethanol (1.8 g/kg, i.p.) or saline treatments daily for 15 consecutive days, followed by treatment with carbetocin (0.64 mg/kg, i.p.) or a vehicle for 6 days. Subsequently, on day 22, all the animals underwent an ethanol challenge to assess the expression of behavioral sensitization. The plasma corticosterone levels were measured on days 21 and 22. The CBT effectively prevented the expression of ethanol-induced behavioral sensitization in both male and female subjects, with no alterations having been detected in their corticosterone levels. In the ethanol consumption study, following an initial phase of ethanol acquisition, the male mice underwent a 6-day treatment with CBT i.p. or saline before being re-exposed to ethanol. We also found a reduction in their ethanol consumption due to the CBT treatment. In conclusion, carbetocin emerges as a promising and effective intervention for mitigating ethanol-induced behavioral sensitization and reducing ethanol intake, highlighting its potential significance in alcohol addiction treatment.

RESUMO

Introduction: The aim of the present study was to investigate the behavioral effects of the benzodiazepine midazolam in male mice, in models of anxiolysis, learning, and abuse-related effects. Methods: In a first set of experiments, male Swiss mice were submitted to the training session of a discriminative avoidance (DA) task on the elevated plus maze to evaluate anxiety-like behavior and learning after vehicle or midazolam (1, 2 or 5 mg/kg, i.g.) administration. The same animals were submitted to a conditioned place preference (CPP) protocol with midazolam (1, 2 or 5 mg/kg, i.g.). In a second experiment, outbred (Swiss) and inbred (C57BL/6) male mice were submitted to a two-bottle choice (TBC) oral midazolam drinking procedure. Animals were exposed to one sucrose bottle and one midazolam (0.008, 0.016 or 0.032 mg/ml) plus sucrose bottle. Results: Midazolam (1 and 2 mg/kg) induced anxiolytic-like effects, and all doses of midazolam prevented animals from learning to avoid the aversive closed arm during the DA training session. Assessment of midazolam reward via the CPP procedure and choice via the TBC procedure showed notable variability. A 2-step cluster analysis for the CPP data showed that midazolam data were well-fitted to 2 separate clusters (preference vs. aversion), albeit with the majority of mice showing preference (75%). Correlational and regression analyses showed no relationship between midazolam reward and anxiolytic-like effects (time spent in the open arms in the DA test) or learning/memory. Two-step cluster analysis of the TBC data also demonstrated that, regardless of strain, mice overall fell into two clusters identified as midazolam-preferring or midazolam-avoiding groups. Both midazolam preference and avoidance were concentration-dependent in a subset of mice. Discussion: Our findings show that midazolam preference is a multifactorial behavior, and is not dependent solely on the emergence of therapeutic (anxiolytic-like) effects, learning impairments, or on genetic factors (inbred vs. outbred animals).

RESUMO

Introduction: Clinical and preclinical research on cocaine use disorder (CUD) has shown that sex differences in drug seeking are influenced by hormonal fluctuations. Estradiol (E2), a sex steroid hormone, has been linked to female drug effects, vulnerability to use/abuse, and psychosocial factors. Preclinical studies show that estradiol in females facilitates the extinction of cocaine-seeking behavior indicating a possible role in regulating extinction learning. Similar to females, males' brains contain the aromatase enzyme which converts testosterone to estradiol. However, it is unclear whether estradiol plays a role in male extinction learning as it does in females. Furthermore, how endogenously aromatized estradiol affects drug addiction in males is unknown. Therefore, this study investigated whether endogenous estradiol regulates cocaine seeking in male rats. We hypothesized that decreased aromatase enzyme activity, resulting in decreased estradiol synthesis in male brains, will impair extinction learning leading to increased cocaine-seeking behavior. Methods: This hypothesis was tested using cocaine-conditioned place preference (CPP), and short access self-administration (SA), followed by extinction and reinstatement. Before each extinction session for CPP or SA, male rats received an injection of either 1 (low dose) or 2.5 mg/kg (high dose) of the aromatase inhibitor Fadrozole (FAD), or vehicle. Results: FAD groups showed dose-dependent effects on cocaine-seeking behavior compared to the vehicle group during CPP extinction. Specifically, low dose FAD facilitated extinction of cocaine CPP, whereas high dose FAD impaired it. In contrast, neither dose of FAD had any effects on the extinction of cocaine SA. Interestingly, only the low dose FAD group had decreased active lever pressing during cue- and cocaine-primed reinstatement compared to the vehicle group. Neither dose of FAD had an effect on sucrose extinction or reinstatement of sucrose seeking. Discussion: These results from CPP experiments suggest that estradiol may impact extinction learning, as a low dose of FAD may strengthen the formation of cocaine extinction memory. Additionally, in male rats undergoing cocaine SA, the same low dose of aromatase inhibitor effectively reduced reinstatement of cocaine-seeking behavior. Thus, estradiol impacts cocaine seeking and extinction in both males and females, and it may also influence the development of sex-specific treatment strategies for CUD.

RESUMO

Modafinil (MOD) is a wakefulness promoter used to treat sleep disorders such as narcolepsy and obstructive sleep apnea. Its action mechanism consists in inhibiting dopamine (DAT) and norepinephrine (NET) transporters, but it has no affinity for the serotonin transporter (SERT). Modafinil's addictive potential is not yet clear, but one feature that differentiates it from potentially addictive drugs like cocaine revolves around affinity for SERT. The aims of the present study were to determine whether co-administration of MOD with the selective serotonin reuptake inhibitor citalopram (CIT) can increase MOD's psychostimulant effects on motor activity (MA), verify the effects of subsequent self-administration of MOD mixed with CIT, and document the presence of any symptoms of withdrawal. At 60 postnatal days (PD), male Wistar rats were treated chronically (16 days) with MOD at 30 or 60 mg/kg, with MOD+CIT at four dosage combinations administered to four groups (30MOD + CIT3, 30MOD + CIT5, 60MOD + CIT3, 60MOD + CIT5 mg/kg), or with a vehicle. After 40 min of daily drug administration, MA was measured on the open field test. MA increased only in the 60MOD group. The rats co-administered with 30MOD + 3CIT and 60MOD + 3CIT showed a decrease in the motivation to seek a pleasurable stimulus (lower consumption of sweet solution) after treatment concluded. The 60MOD and 60MOD + 3CIT groups showed MA sensitization after MOD intake. Additionally, higher self-administration of the mixture was observed in the groups pre-treated with 30MOD + 3CIT and 60MOD + 3CIT. Results suggest that serotonergic activity enhances modafinil's psychostimulant effects.

Assuntos

Estimulantes do Sistema Nervoso Central , Citalopram , Animais , Compostos Benzidrílicos/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Citalopram/farmacologia , Proteínas da Membrana Plasmática de Transporte de Dopamina , Masculino , Modafinila/farmacologia , Ratos , Ratos Wistar , Proteínas da Membrana Plasmática de Transporte de Serotonina

RESUMO

RATIONALE: Ayahuasca has been proposed as a potential treatment of alcohol (ethanol) use disorder (AUD). The serotonin 5-HT2A receptor agonist N,N-dimethyltryptamine (DMT) is the main psychoactive component of ayahuasca, suggesting that its therapeutic effects may be mediated by 5-HT2A receptors. OBJECTIVES: The aim of the present study was to investigate the effects of ayahuasca on the expression of ethanol self-administration using a two-bottle choice procedure and the role of 5-HT2A receptors in those effects. METHODS: Male mice had intermittent access to ethanol (10% v/v) in a two-bottle choice procedure for 30 days. Animals were then submitted to 3 treatment phases, each followed by ethanol re-exposure tests. During the treatment phase, every 3 days, animals received i.p. injections of either vehicle or the 5-HT2A receptor antagonist M100907 (M100, 1 mg/kg) followed by an i.g. (gavage) administration of vehicle or ayahuasca (100 mg/kg) and were exposed to the self-administration apparatus with no ethanol availability. During re-exposure tests, animals were submitted to the same conditions as during acquisition, with no treatments prior to those sessions. RESULTS: Treatment with ayahuasca blocked the expression of ethanol self-administration, decreasing ethanol intake and preference during re-exposure tests. Pretreatment with M100 blocked the effects of ayahuasca on ethanol drinking without significantly attenuating ethanol self-administration. CONCLUSIONS: Treatment with ayahuasca during alcohol abstinence blocked the expression of alcohol self-administration in mice, and 5-HT2A receptor activation is critical for those effects to emerge. Our findings support a potential for ayahuasca and other 5-HT2A receptor agonists as adjunctive pharmacotherapies for the treatment of AUD.

Assuntos

Banisteriopsis , Consumo de Bebidas Alcoólicas/tratamento farmacológico , Animais , Etanol/farmacologia , Masculino , Camundongos , N,N-Dimetiltriptamina , Receptor 5-HT2A de Serotonina , Serotonina

RESUMO

Actin dynamics in dendritic spines can be associated with the neurobiological mechanisms supporting the comorbidity between stress exposure and cocaine increase rewards. The actin cytoskeleton remodeling in the nucleus accumbens (NA) has been implicated in the expression of stress-induced cross-sensitization with cocaine. The present study evaluates the involvement of cofilin, a direct regulator of actin dynamics, in the impact of stress on vulnerability to cocaine addiction. We assess whether the neurobiological mechanisms that modulate repeated-cocaine administration also occur in a chronic restraint stress-induced cocaine self-administration model. We also determine if chronic stress induces alterations in dendritic spines through dysregulation of cofilin activity in the NA core. Here, we show that the inhibition of cofilin expression in the NA core using viral short-hairpin RNA is sufficient to prevent the cocaine sensitization induced by chronic stress. The reduced cofilin levels also impede a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor surface expression enhancement and promote the reduction of head diameter in animals pre-exposed to stress after a cocaine challenge in the NA core. Moreover, downregulation of cofilin expression prevents facilitation of the acquisition of cocaine self-administration (SA) in male rats pre-exposed to chronic stress without modifying performance in sucrose SA. These findings reveal a novel, crucial role for cofilin in the neurobiological mechanisms underpinning the comorbidity between stress exposure and addiction-related disorders.

RESUMO

Estudio transversal que describe preferencias y satisfacción hacia un programa de tamizaje de cáncer cervical con pruebas rápidas autoadministradas, para la detección del virus de papiloma humano (VPH). De las 2090 usuarias captadas por el programa en Ventanilla Callao-Perú, se seleccionó aleatoriamente a 97 para ser encuestadas. Asimismo, se realizaron entrevistas a mujeres líderes de la comunidad, encargadas de ofrecer las pruebas. El 74,2% de las usuarias se sintió, cuanto menos, satisfecha con el programa. El 68% de las mujeres prefiere la autotoma de la prueba, principalmente por demandar menos tiempo. De las mujeres que prefieren la toma en el centro de salud, el 90,3% lo hace por la seguridad de que la prueba sea realizada correctamente. La inclusión de líderes comunitarias en el programa permitió una buena difusión de la prueba y de los pasos para realizarla.

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Cross-sectional study describing preferences and satisfaction towards a cervical cancer screening program with selfadministered rapid tests for the detection of human papillomavirus (HPV). Of 2 090 users picked by the program in Ventanilla Callao - Peru, 97 were randomly selected to be surveyed. In addition, interviews were conducted with women leaders of the community, in charge of providing the evidence. 74.2% of the users felt, at least, satisfied with the program. 68% of women prefer to take the test, mainly by demanding less time. Of women who prefer to take the test at the Health Center, 90.3% do so for the safety of the test being done correctly. The inclusion of community leaders in the program allowed a good diffusion of the test and the steps to carry it out.

Assuntos

Adulto , Feminino , Humanos , Pessoa de Meia-Idade , Papillomaviridae/isolamento & purificação , Autocuidado , Neoplasias do Colo do Útero/diagnóstico , Neoplasias do Colo do Útero/virologia , Detecção Precoce de Câncer/métodos , Preferência do Paciente , Estudos Transversais , Satisfação do Paciente

RESUMO

GABAA receptor positive allosteric modulators (GABAA receptor modulators) are commonly used for the treatment of insomnia. Nevertheless, the effects of these compounds on psychostimulant-induced sleep impairment are poorly understood. Because GABAA receptor modulators have been shown to decrease the abuse-related effects of psychostimulants, the aim of the present study was to evaluate the effects of temazepam (0.3, 1.0 or 3.0 mg/kg) and eszopiclone (0.3, 1.0 or 3.0 mg/kg), two GABAA receptor modulators, on the behavioral neuropharmacology of methamphetamine in adult rhesus macaques (n = 5). Sleep-like measures and general daytime activity were evaluated with Actiwatch monitors. Methamphetamine self-administration (0.03 mg/kg/inf) was evaluated during morning sessions. Methamphetamine-induced dopamine overflow was assessed through in vivo microdialysis targeting the nucleus accumbens. Nighttime treatment with either temazepam or eszopiclone was ineffective in improving sleep-like measures disrupted by methamphetamine self-administration. Acute pretreatment with a low dose of temazepam before self-administration sessions increased methamphetamine self-administration without affecting normal daytime home-cage activity. At a high dose, acute temazepam pretreatment decreased methamphetamine self-administration and attenuated methamphetamine-induced increases in dopamine in the nucleus accumbens, without decreasing general daytime activity. Acute eszopiclone treatment exerted no effects on methamphetamine intake or drug-induced increases in dopamine. Our study suggests that treatments based on GABAA receptor modulators are not effective for the treatment of sleep disruption in the context of psychostimulant use. In addition, distinct GABAA receptor modulators differentially modulated the abuse-related effects of methamphetamine, with acute treatment with the high efficacy GABAA receptor modulator temazepam decreasing the behavioral and neurochemical effects of methamphetamine.

Assuntos

Transtornos Relacionados ao Uso de Anfetaminas/tratamento farmacológico , Dopamina/metabolismo , Zopiclona/farmacologia , Agonistas de Receptores de GABA-A/farmacologia , Sono/efeitos dos fármacos , Temazepam/farmacologia , Transtornos Relacionados ao Uso de Anfetaminas/metabolismo , Animais , Estimulantes do Sistema Nervoso Central/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Macaca mulatta , Masculino , Metanfetamina/administração & dosagem , Receptores de GABA-A/metabolismo , Autoadministração

RESUMO

BACKGROUND: Relapse to cocaine use is a major problem in the clinical treatment of cocaine addiction. Antidepressants have been studied for their therapeutic potential to treat cocaine use disorder. Research has suggested that antidepressants attenuate both drug craving and the re-acquisition of drug-seeking and drug-taking behaviors. This study examined the efficacy of mirtazapine, an antidepressant/anxiolytic, in decreasing cocaine seeking in rats. METHODS: We used the cocaine self-administration paradigm to assess the effects of mirtazapine on rats trained to self-administer cocaine or food under a fixed-ratio schedule. Mirtazapine (30 mg/kg, i.p.) was administered during extinction. RESULTS: Mirtazapine significantly attenuated non-reinforced lever-press responses during extinction. Moreover, the mirtazapine dosed for 30 days during extinction produced sustained attenuation of lever-press responses during re-acquisition of cocaine self-administration, without changing food-seeking behavior. Our results showed that mirtazapine attenuated the re-acquisition of cocaine-seeking responses. CONCLUSION: Our study pointed to the efficacy of mirtazapine in reducing the risk of drug relapse during abstinence, suggesting for its potential use as a novel pharmacological agent to treat drug abuse.

Assuntos

Anestésicos Locais/administração & dosagem , Antidepressivos Tricíclicos/farmacologia , Cocaína/administração & dosagem , Condicionamento Operante/efeitos dos fármacos , Comportamento de Procura de Droga/efeitos dos fármacos , Mianserina/análogos & derivados , Análise de Variância , Animais , Extinção Psicológica/efeitos dos fármacos , Alimentos , Masculino , Mianserina/farmacologia , Mirtazapina , Ratos , Ratos Wistar , Esquema de Reforço , Autoadministração , Fatores de Tempo

RESUMO

RATIONALE: The abuse of the psychostimulant methamphetamine (MA) is associated with substantial costs and limited treatment options. To understand the mechanisms that lead to abuse, animal models of voluntary drug intake are crucial. OBJECTIVES: We aimed to develop a protocol to study long-term non-invasive voluntary intake of MA in mice. METHODS: Mice were maintained in their home cages and allowed daily 1 h access to an attached tunnel leading to a test chamber in which nebulized MA was available. Restated, if they went to the nebulizing chamber, they self-administered MA by inhalation. This protocol was compared to injected and to imposed exposure to nebulized MA, in a series of seven experiments. RESULTS: We established a concentration of nebulized MA at which motor activity increases following voluntary intake resembled that following MA injection and imposed inhalation. We found that mice regulated their exposure to MA, self-administering for shorter durations when concentrations of nebulized MA were increased. Mice acquire the available MA by repeatedly running in and out of the nebulizing chamber for brief bouts of intake. Such exposure to nebulized MA elevated plasma MA levels. There was limited evidence of sensitization of locomotor activity. Finally, blocking access to the wheel did not affect time spent in the nebulizing chamber. CONCLUSIONS: We conclude that administration of MA by nebulization is an effective route of self-administration, and our new protocol represents a promising tool for examining the transitions from first intake to long-term use and its behavioral and neural consequences in a non-invasive protocol.

Assuntos

Administração por Inalação , Estimulantes do Sistema Nervoso Central/administração & dosagem , Metanfetamina/administração & dosagem , Autoadministração , Animais , Comportamento Animal/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Masculino , Metanfetamina/farmacologia , Camundongos , Modelos Animais , Atividade Motora/efeitos dos fármacos , Nebulizadores e Vaporizadores , Corrida , Fatores de Tempo

RESUMO

ABSTRACT Objective: to analyze the self-care competence in the administration of insulin performed by older people aged 70 or over. Method: cross-sectional study carried out with 148 older people aged 70 or over, who performed self-administration of insulin. Data collection was carried out using a structured questionnaire and an adapted guide for the application of the Scale to Identify Self-Care Competence of Patients with Diabetes, at the participants' home. Data analysis included descriptive and inferential statistical tests, with forward logistic regression. Results: the prevalence of self-care competence in the administration of insulin was 35.1%. Handwashing error was the most frequent in self-administration of insulin. Self-care competence was negatively associated with retirees and positively associated with senior patients who performed capillary blood glucose monitoring and skin pinching during insulin application. Conclusion: there was low self-care competence and it was associated with both the sociodemographic and the clinical characteristics with regard to self-application of insulin by the older people.

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RESUMO Objetivo: analisar a competência para o autocuidado na administração de insulina por idosos septuagenários ou mais de idade. Método: estudo transversal, com 148 idosos septuagenários ou mais de idade, que realizavam autoadministração de insulina. A coleta de dados deu-se por meio de questionário estruturado e guia adaptado para aplicação da Escala para Identificação da Competência do Diabético para o Autocuidado, no domicílio dos participantes. Na análise dos dados, foram compreendidos testes estatísticos descritivos e inferenciais, com regressão logística forward. Resultados: a prevalência da competência para o autocuidado na administração de insulina foi de 35,1%. Lavagem das mãos foi o erro mais frequente na autoaplicação de insulina. A competência para o autocuidado apresentou associação negativa para os aposentados e associação positiva para os idosos que realizavam glicemia capilar e prega subcutânea, durante a aplicação de insulina. Conclusão: a competência para o autocuidado foi baixa e esteve associada tanto às características sociodemográficas e clínicas quanto ao desempenho do idoso para a autoaplicação de insulina.

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RESUMEN Objetivo: analizar la capacidad de autocuidado en la administración de insulina en adultos mayores de 70 años de edad o más. Método: estudio transversal realizado con 148 adultos mayores de 70 años de edad o más, que realizaban la autoadministración de insulina. La recolección de datos se llevó a cabo mediante un cuestionario estructurado y una guía adaptada para la aplicación de la Escala para la Identificación de la Capacidad de Autocuidado de Pacientes con Diabetes, en el hogar de los participantes. En el análisis de los datos, se incluyeron pruebas estadísticas descriptivas e inferenciales, con regresión logística forward. Resultados: la prevalencia de capacidad de autocuidado en la administración de insulina fue del 35,1%. El error en el lavado de manos fue el más frecuente en la autoadministración de insulina. La capacidad de autocuidado se asoció negativamente con los jubilados y se asoció positivamente con los adultos mayores que realizaban la monitorización de la glucemia capilar y el pellizco en la piel durante la aplicación de la insulina. Conclusión: la capacidad de autocuidado fue baja y se asoció con las características sociodemográficas y clínicas con respecto a la auto-aplicación de la insulina por los adultos mayores.

Assuntos

Humanos , Masculino , Feminino , Idoso , Autocuidado , Diabetes Mellitus/tratamento farmacológico , Hipoglicemiantes/administração & dosagem , Insulina/administração & dosagem , Autoadministração , Estudos Transversais

RESUMO

Alcohol is the most commonly used and abused substance worldwide. The emergence of alcohol use disorders, and alcohol dependence in particular, is accompanied by functional changes in brain reward and stress systems, which contribute to escalated alcohol drinking and seeking. Corticotropin-releasing factor (CRF) systems have been critically implied in the transition toward problematic alcohol drinking and alcohol dependence. This review will discuss how dysregulation of CRF function contributes to the vulnerability for escalated alcohol drinking and other consequences of alcohol consumption, based on preclinical evidence. CRF signaling, mostly via CRF1 receptors, seems to be particularly important in conditions of excessive alcohol taking and seeking, including during early and protracted withdrawal, relapse, as well as during withdrawal-induced anxiety and escalated aggression promoted by alcohol. Modulation of CRF1 function seems to exert a less prominent role over low to moderate alcohol intake, or to species-typical behaviors. While CRF mechanisms in the hypothalamic-pituitary-adrenal axis have some contribution to the neurobiology of alcohol abuse and dependence, a pivotal role for extra-hypothalamic CRF pathways, particularly in the extended amygdala, is well characterized. More recent studies further suggest a direct modulation of brain reward function by CRF signaling in the ventral tegmental area, nucleus accumbens, and the prefrontal cortex, among other structures. This review will further discuss a putative role for other components of the CRF system that contribute for the overall balance of CRF function in reward and stress pathways, including CRF2 receptors, CRF-binding protein, and urocortins, a family of CRF-related peptides.

RESUMO

RATIONALE: Caffeine is one of the psychoactive substances most widely used as an adulterant in illicit drugs, such as cocaine. Animal studies have demonstrated that caffeine is able to potentiate several cocaine actions, although the enhancement of the cocaine reinforcing property by caffeine is less reported, and the results depend on the paradigms and experimental protocols used. OBJECTIVES: We examined the ability of caffeine to enhance the motivational and rewarding properties of cocaine using an intravenous self-administration paradigm in rats. Additionally, the role of caffeine as a primer cue during extinction was evaluated. METHODS: In naïve rats, we assessed (1) the ability of the cocaine (0.250-0.125 mg/kg/infusion) and caffeine (0.125-0.0625 mg/kg/infusion) combination to maintain self-administration in fixed ratio (FR) and progressive ratio (PR) schedules of reinforcement compared with cocaine or caffeine alone and (2) the effect of caffeine (0.0625 mg/kg/infusion) in the maintenance of responding in the animals exposed to the combination of the drugs during cocaine extinction. RESULTS: Cocaine combined with caffeine and cocaine alone was self-administered on FR and PR schedules of reinforcement. Interestingly, the breaking point determined for the cocaine + caffeine group was significantly higher than the cocaine group. Moreover, caffeine, that by itself did not maintain self-administration behavior in naïve rats, maintained drug-seeking behavior of rats previously exposed to combinations of cocaine + caffeine. CONCLUSIONS: Caffeine enhances the reinforcing effects of cocaine and its motivational value. Our results highlight the role of active adulterants commonly used in cocaine-based illicit street drugs.

Assuntos

Cafeína/farmacologia , Estimulantes do Sistema Nervoso Central/farmacologia , Cocaína/administração & dosagem , Condicionamento Operante , Inibidores da Captação de Dopamina/administração & dosagem , Comportamento de Procura de Droga/efeitos dos fármacos , Motivação/efeitos dos fármacos , Recompensa , Animais , Masculino , Ratos , Ratos Sprague-Dawley , Esquema de Reforço , Reforço Psicológico , Autoadministração

RESUMO

O envelhecimento populacional, o aumento da prevalência de diabetes em idosos e o aumento da utilização de insulina no tratamento de diabetes tipo 2, demonstram a necessidade de estudos para orientar abordagens de cuidados para idosos insulinizados. O que se observa no cotidiano de vida do idoso é que as ações que envolvem o autocuidado para o controle da glicemia, como autoaplicação de insulina e automonitorização glicêmica, nem sempre são manejadas de forma adequada, dificultando o controle e expondo o idoso a maiores riscos de complicações crônicas e agudas. A prática de autoadministração de insulina pode sofrer interferências de diversos fatores, como incapacidades cognitivas, deficiências e perda de autonomia e independência, muito comuns em idosos e que precisam ser investigados para serem trabalhados e minimizados pela atuação dos profissionais de saúde. OBJETIVO: Analisar a competência para o autocuidado na administração de insulina por septuagenários ou mais idosos com Diabetes Mellitus (DM). METODOLOGIA: Trata-se de um estudo transversal, realizado por meio de visitas domiciliares, com 148 septuagenários ou mais idosos que adquiriram insulina em algum dos centros de saúde do distrito Noroeste de Belo Horizonte e que realizam a autoadministração domiciliar desse medicamento. Foi realizada a coleta de dados sóciodemográficos e clínicos dos idosos e registro das alterações nas capacidades físicas, mentais e motivacionais. No segundo momento ocorreu a observação no domicílio do processo de autoadministração de insulina e o registro dos erros e acertos encontrados. Para a avaliação das capacidades, foi utilizada a Escala para Identificação da Competência do Diabético para o Autocuidado, proposta por NUNES (1982). RESULTADOS: O perfil dos idosos caracterizou-se como uma população predominantemente feminina (64,2%), proveniente do interior de Minas Gerais (61,5%), sem cônjuge (54,7%), com escolaridade menor ou igual a 4 anos de estudo (59,5%)...

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The aging population, the increasing prevalence of diabetes in the elderly and increased use of insulin to treat type 2 diabetes demonstrate the need for studies to guide approaches to care for elderly insulinized. What is observed in the elderly routine is that actions involving self-care to control blood sugar, such as self-administration of insulin and blood glucose monitoring, are not always managed properly, making it difficult to control and expose the elderly to greater risks of acute and chronic complications. The practice of self-administration of insulin may suffer interference from several factors, such as cognitive impairment, disability and loss of autonomy and independence, very common in the elderly, that need to be investigated in order to be worked out and minimized the role of health professionals. OBJECTIVE: To assess the competence for self-care insulin administration by septuagenarian or more older with diabetes. METHODOLOGY: This is a cross-sectional study, carried out through home visits, with 148 septuagenarian or more older who acquired insulin in any of the health centers in the Northwest district of Belo Horizonte and conducting the home self-administration of this drug. Collecting sociodemographic and clinical data of elderly and record of changes in the physical, mental and motivational was held. The second time was the observation of insulin self-administration process and registration of errors and hits found. For the assessment of capabilities, we used the Scale for Diabetic Racing identification for self-care, proposed by NUNES (1982). RESULTS: The profile of the elderly was characterized as a predominantly female population (64.2%), from the country side of Minas Gerais (61.5%), with no spouse (54.7%), with less than or equal to 4 years education study (59.5%). The predominant age group was 70 to 79 years (73.6%). In the evaluation of errors in insulin self-administration, the...

Assuntos

Humanos , Idoso , Idoso de 80 Anos ou mais , Autocuidado , Diabetes Mellitus/tratamento farmacológico , Idoso , Insulina , Autoadministração

RESUMO

Amphetamine (AMPH) is an addictive psychostimulant drug whose use has been related to neurotoxicity. Experimentally, AMPH increases anxiety-like symptoms, showing addictive properties. In the last decades, the growing consumption of processed foods has provided an excess of saturated and trans fats in detriment of essential fatty acids, which may modify the lipid profile of brain membranes, thus modifying its permeability and dopaminergic neurotransmission. Here, we assessed the influence of brain incorporation of different fatty acids (FA) on AMPH self-administration. Three groups of young male rats were orally supplemented from weaning with a mixture of soybean oil (SO, rich in n-6 FA) and fish oil (FO, rich in n-3 FA), hydrogenated vegetable fat (HVF, rich in trans fatty acids--TFA), or water (control group). These animals were born from dams that were supplemented with the same fat from pregnancy to lactation. Anxiety-like symptoms and locomotor index were assessed in elevated plus maze and open-field (OF), respectively, while brain molecular expressions of dopaminergic receptors, dopamine transporter (DAT), and BDNF were determined in the cortex and hippocampus. HVF increased the frequency of AMPH self-administration and was associated with reinforcement and withdrawal signs as observed by increased anxiety-like symptoms. Contrarily, SO/FO decreased these parameters. Increased BDNF protein together with decreased DAT expression was observed in the hippocampus of HVF group. Based on these findings, our study points to a harmful influence of trans fats on drug addiction and craving symptoms, whose mechanism may be related to changes in the dopaminergic neurotransmission.

Assuntos

Anfetamina/farmacologia , Córtex Cerebral/efeitos dos fármacos , Córtex Cerebral/metabolismo , Comportamento de Procura de Droga/fisiologia , Ácidos Graxos trans/farmacologia , Animais , Ansiedade/induzido quimicamente , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Proteínas da Membrana Plasmática de Transporte de Dopamina/metabolismo , Feminino , Óleos de Peixe/farmacologia , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Atividade Motora/efeitos dos fármacos , Gravidez , Ratos , Ratos Wistar , Receptores de Dopamina D1/metabolismo , Receptores de Dopamina D2/metabolismo , Autoadministração , Óleo de Soja/farmacologia , Fatores de Tempo

RESUMO

This review analyzes literature that describes the behavioral effects of 2 metabolites of ethanol (EtOH): acetaldehyde and salsolinol (a condensation product of acetaldehyde and dopamine) generated in the brain. These metabolites are self-administered into specific brain areas by animals, showing strong reinforcing effects. A wealth of evidence shows that EtOH, a drug consumed to attain millimolar concentrations, generates brain metabolites that are reinforcing at micromolar and nanomolar concentrations. Salsolinol administration leads to marked increases in voluntary EtOH intake, an effect inhibited by mu-opioid receptor blockers. In animals that have ingested EtOH chronically, the maintenance of alcohol intake is no longer influenced by EtOH metabolites, as intake is taken over by other brain systems. However, after EtOH withdrawal brain acetaldehyde has a major role in promoting binge-like drinking in the condition known as the "alcohol deprivation effect"; a condition seen in animals that have ingested alcohol chronically, are deprived of EtOH for extended periods, and are allowed EtOH re-access. The review also analyzes the behavioral effects of acetate, a metabolite that enters the brain and is responsible for motor incoordination at low doses of EtOH. Also discussed are the paradoxical effects of systemic acetaldehyde. Overall, evidence strongly suggests that brain-generated EtOH metabolites play a major role in the early ("first-hit") development of alcohol reinforcement and in the generation of relapse-like drinking.

Assuntos

Acetaldeído/metabolismo , Acetaldeído/farmacologia , Encéfalo/metabolismo , Comportamento de Procura de Droga/efeitos dos fármacos , Etanol/metabolismo , Etanol/farmacologia , Isoquinolinas/metabolismo , Reforço Psicológico , Acetaldeído/administração & dosagem , Acetatos/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Isoquinolinas/administração & dosagem , Isoquinolinas/farmacologia , Autoadministração

RESUMO

A investigação de plantas medicinais como recurso terapêutico para combater o alcoolismo ainda é muito insipiente com poucas espécies investigadas. No presente trabalho avaliamos o efeito do extrato hidroalcoólico das folhas da planta Piper caldense C. DC. com relação ao consumo de álcool e também a sua potencialidade ansiolítica. Foram utilizados ratos Wistar machos, os quais foram divididos em grupos controle (solução fisiológica) e tratado (extrato da planta nas doses de 25, 50 e 150 mg/kg, e diazepam 2 mg/kg). Os animais foram tratados através da via intraperitoneal 1 h antes dos experimentos. Os modelos animais utilizados foram: Labirinto em Cruz Elevado (LCE) e auto-administração de álcool (AA). No LCE o extrato não apresentou efeito ansiolítico do tipo benzodiazepínico. Por outro lado, no comportamento relacionado a auto-administração de solução de álcool, o extrato apresentou efeito significativo reduzindo o consumo de álcool em relação ao grupo controle. Apesar do extrato não ter apresentado efeito ansiolítico, o mesmo parece apresentar potencialidades para combater o abuso e a dependência de álcool.

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The investigation of medicinal plants as therapeutic resources in the combat of alcoholism is still very incipient with few species being investigated. The purpose of the present study was to examine the effects of the hydroalcoholic extract of leaves of Piper caldense C. DC. in relation to alcohol consumption and also its anxiolytic potentiality. Male Wistar rats, which had been separated into control group (saline) and treated group (Plant extract doses of 25, 50 and 150 mg/kg and 2 mg/kg of diazepam), were used. Animals were injected intraperitoneally 1 h before the tests. The following models were used: Elevated plus maze (EPM) and alcohol self-administration (ASA). In the EPM, the extract did not show benzodiazepine anxiolytic effect. On the other hand, in the behavior related to alcohol self-administration, the extract showed a significant effect, reducing alcohol consumption compared to the control group. Although the extract has not shown any anxiolytic effect, the results suggest that the plant has potential to combat alcohol abuse and addiction.

Assuntos

Animais , Masculino , Ratos , Plantas Medicinais/anatomia & histologia , Consumo de Bebidas Alcoólicas/fisiopatologia , Extratos Vegetais/análise , Piperaceae/anatomia & histologia , Ratos , Terapêutica/classificação

RESUMO

Introducción: La necesidad insatisfecha de anticoncepción sigue siendo alta en el Perú y a nivel mundial. La asesoría adecuada del profesional de la salud ha demostrado maximizar el uso y cumplimiento de métodos anticonceptivos que se ajusten a las necesidades de cada mujer. Objetivos: Medir el impacto de la asesoría brindada por profesionales de salud ginecoobstetras en la elección de un método anticonceptivo hormonal de autoadministración -píldora diaria, parche transdérmico semanal y anillo vaginal mensual-, así como los factores determinantes de ello. Diseño: Estudio observacional, descriptivo y transversal. Lugar: Lima, Piura, Chiclayo y Trujillo, Perú. Institución: Proyecto Latinoamericano PIENSA: Programa de Investigación y Educación en Salud Anticonceptiva. Participantes: Quinientos ochenta y un mujeres de 18 a 40 años que acudieron a la consulta de 40 ginecoobstetras que brindaron asesoría sobre métodos anticonceptivos. Intervenciones: Se realizó una asesoría estandarizada con material didáctico que contenía información sobre efectividad, mecanismo de acción, modo de uso, beneficios y riesgos, así como idoneidad, respecto a las necesidades individuales. Principales medidas de resultados: Elección original y elección final del método anticonceptivo luego de la asesoría, y factores involucrados. Resultados: La elección inicial del método fue de 57% la píldora, 15% el anillo vaginal y 13% el parche transdérmico; luego de la asesoría fue: 38% la píldora, 33% el anillo vaginal, y 19% el parche transdérmico. Resultó estadísticamente significativa la preferencia entre las usuarias del anillo vaginal de 15% a 33% y la preferencia del parche transdérmico de 13 a 19%; p<0,005. La razón principal para la elección del método fue la facilidad de uso. Conclusiones: Las mujeres peruanas participantes del proyecto PIENSA eligieron inicialmente la píldora diaria, cuyo porcentaje disminuyó luego de la asesoría por un profesional de la salud. Asimismo, el número de mujeres que eligieron los métodos de parche transdérmico y anillo vaginal se incrementó significativamente.

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Introduction: Unmet needs for contraception are high in Peru and worldwide. Proper advice from health professionals maximizes use and compliance of contraceptive methods meeting the needs of every woman. Objectives: To determine the impact and determinant factors of gynecologists advice for women choosing a self-administered hormonal contraceptive method, either daily pill, weekly transdermal patch or monthly vaginal ring. Design: Observational, descriptive and transversal study. Location: Lima, Piura, Chiclayo, and Trujillo, Peru. Institution: Latin Project PIENSA: Program for Research and Education on Contraceptive Health. Participants: Five hundred eighty-one women aged 18 to 40 attended by 40 gynecologists providing advice on contraception. Interventions: Standardized counseling with educational material including information on effectiveness, mechanism of action, user mode, benefits and risks as well as suitability in regards to individual needs was conducted. Main outcome measures: Original choice and final election of contraceptive method following counseling as well as factors involved. Results: Initial method choice was 57% for the pill, 15% for the vaginal ring, and 13% for transdermal patch. Following advice election was for pill 38%, vaginal ring 33%, and transdermal patch 19%. Statistically significant preference from 15% to 33% was found in vaginal ring users, and 13% to 19% for transdermal patch; p <0,005. The main reason for methods choice was ease of use. Conclusions: Peruvian women participating in PIENSA Project initially chose the daily contraceptive pill; but this election decreased following health professional counseling. The number of women who chose transdermal patch and vaginal ring increased significantly.