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To compare outcomes between autologous fascia lata and autologous hamstring grafts for chronic pectoralis major muscle (PMM) rupture repair, and perform histological, and imaging analyses. Forty male patients with chronic PMM ruptures (time since injury ranging from >3 months to 5 years) and a mean age of 37.3 years (SD = 9.7 years) were evaluated. One group (20 patients) received an autologous semitendinosus graft, and another group (20 patients) received an autologous fascia lata graft for PMM reconstruction. These patients with fascia lata grafts by Bak 2criterium 60% of the patients presented excellent results, 20% presented good results, 15% presented fair results, and 5% presented poor results. In the hamstring group 65% of the patients presented excellent results, 30% presented good results, and 5% presented fair results. In this comparative study, no difference was observed regarding the functional result, image, and histology between groups.
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This study presented a pioneering investigation of the changes in the magnetic resonance imaging images of pectoralis major muscle (PMM) tendon rupture. In all, 26 men were evaluated with acute total PMM rupture (<3 months since injury) with a mean age of 37.3 years (SD = 9.7 years) and 10 control patients with a mean age of 32.6 years (SD = 4.2 years). The evaluation of the tendon PMM injuries was based on the magnetic resonance imaging exam and the histological analysis. The magnetic resonance imaging of the surgically showed two (7.1%) contralateral sides were normal, 16 (57.1%) showed superior tendinopathy, and 10 (35.7%) had total tendinopathy. Inferior tendinopathy was not observed. The tendon histology revealed degenerative changes in 16 (66.7%) fragments, with 12 (50.0%) considered as mild (<25%), and four considered as (16.7%) high (>50.0%) tendinopathy. Total acute rupture of the PMM tendon among weightlifters might be associated with tendinous degeneration prior to injury.
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Introduction: Adolescence is marked by physiological and social changes, such as puberty, increased responsibilities and earlier school start times. This often leads to insufficient sleep on school nights and the need to compensate for lost sleep on weekends, causing a misalignment between biological and social times, which has been termed social jetlag (SJL). SJL triggers stress responses and is associated with several negative health outcomes, including higher cardiometabolic risk in adults. In adolescence, however, SJL has only been consistently related to increases in adiposity but its association with other cardiometabolic indicators are unclear. Method: In a sample of 278 healthy early adolescents (9-15 years of age; 168 girls) we investigated: 1) whether self-reported SJL is associated (using path analyses) with a cardiometabolic status latent factor obtained by testing the best fitting model via confirmatory factor analyses from an initial set of eight indicators [body mass index (BMI), waist/height ratio, triglyceride concentration, diastolic and systolic blood pressure, glycated hemoglobin, total cholesterol/high-density lipoprotein ratio (chol/HDL), and % body fat]; and 2) whether age and/or pubertal status influence the association between SJL and cardiometabolic status. Result: We found that, for girls, higher SJL was associated with more adverse cardiometabolic latent scores (the shared variance of BMI, waist/height ratio, chol/HDL and systolic blood pressure, which had acceptable model fit indices). However, the role of age and pubertal status in this association was unclear for both sexes. Discussion: SJL was associated with adverse cardiometabolic latent traits beyond increases in adiposity in this observational study in early female adolescents. Because disruptions of circadian rhythms are believed to lead to dysregulated energy homeostasis and not vice-versa, our findings highlight the need for sleep interventions in adolescence to help reduce the global burden of cardiometabolic ill health, especially in girls.
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Doenças Cardiovasculares , Obesidade , Masculino , Adulto , Humanos , Adolescente , Feminino , Obesidade/complicações , Sono/fisiologia , Índice de Massa Corporal , Síndrome do Jet Lag/complicações , Doenças Cardiovasculares/etiologiaRESUMO
Pectoralis major muscle tendon ruptures associated with physical activity or effort are no longer uncommon in the medical literature. Treatment has also evolved significantly in the last 20 years. However, simultaneous bilateral rupture has only been described in a few cases. This article reports three cases with simultaneous bilateral rupture and describes the examinations and treatment performed. Bilateral lesions, although infrequent, also require early diagnosis and treatment in the acute phase. The chronic phase requires tendon grafting for full correction and a slow rehabilitation process.
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Objective To evaluate the electrophysiological activity of the injured pectoralis major (PM) muscle of operated patients who perform weightlifting, more specifically bench press exercises, especially the activity of the clavicular and sternocostal portions of the PM. Methods All athletes in study I (10 patients) had unilateral complete ruptures during bench press exercises and a history of use of anabolic steroids, an association that is described in up to 86.7% of PM tendon ruptures. The control group included 10 men without PM tendon injury who did not perform bench press exercises. Description of the cross-sectional design. The p -values were obtained by multiple comparisons with Bonferroni correction. Results In the comparison between the control (C) group and the weightlifters during the postoperative period (POS), we found no evidence of differences in any measurements obtained in the clavicular and sternocostal portions of the PM muscle: clavicular average level ( p = 0.847); clavicular standard deviation (SD) ( p = 0.777); clavicular area ( p = 0.933); clavicular median ( p = 0.972); sternocostal average level ( p = 0.633); sternocostal SD ( p = 0.602); sternocostal area ( p = 0.931); and sternocostal median ( p = 0.633). Conclusion In the present study, the electromyographic activity of the PM muscle in weightlifters (bench press exercise) who underwent surgery was within the normal parameters for the clavicular and sternocostal portions studied.
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Abstract Objective To evaluate the electrophysiological activity of the injured pectoralis major (PM) muscle of operated patients who perform weightlifting, more specifically bench press exercises, especially the activity of the clavicular and sternocostal portions of the PM. Methods All athletes in study I (10 patients) had unilateral complete ruptures during bench press exercises and a history of use of anabolic steroids, an association that is described in up to 86.7% of PM tendon ruptures. The control group included 10 men without PM tendon injury who did not perform bench press exercises. Description of the cross-sectional design. The p-values were obtained by multiple comparisons with Bonferroni correction. Results In the comparison between the control (C) group and the weightlifters during the postoperative period (POS), we found no evidence of differences in any measurements obtained in the clavicular and sternocostal portions of the PM muscle: clavicular average level (p = 0.847); clavicular standard deviation (SD) (p = 0.777); clavicular area (p = 0.933); clavicular median (p = 0.972); sternocostal average level (p = 0.633); sternocostal SD (p = 0.602); sternocostal area (p = 0.931); and sternocostal median (p = 0.633). Conclusion In the present study, the electromyographic activity of the PM muscle in weightlifters (bench press exercise) who underwent surgery was within the normal parameters for the clavicular and sternocostal portions studied.
Resumo Objetivo Avaliar a atividade eletrofisiológica do músculo peitoral maior (PM) lesionado de pacientes operados que realizam halterofilismo, mais especificamente exercícios de supino, especialmente a atividade das porções clavicular e esternocostal do PM. Métodos Todos os atletas no estudo I (10 pacientes) tiveram rupturas completas unilaterais durante o exercício de supino, e tinham histórico de uso de esteroides anabolizantes, associação descrita em até 86,7% das rupturas tendinosas do PM. O grupo controle incluiu 10 homens sem lesão no tendão do PM que não realizaram exercícios de supino. Descrição do projeto transversal. Os valores de p foram obtidos por múltiplas comparações com a correção de Bonferroni. Resultados Na comparação entre o grupo controle (C) e os halterofilistas durante o pós-operatório (POS), não foram encontradas diferenças nas medidas obtidas nas porções clavicular e esternocostal do músculo PM: nível médio clavicular (p = 0,847); desvio padrão (DP) clavicular (p = 0,777); área clavicular (p = 0,933); mediana da clavícula (p = 0,972); nível médio esternocostal (p = 0,633); DP esternocostal (p = 0,602); área esternocostal (p = 0,931); e mediana esternocostal (p = 0,633). Conclusão Neste estudo, a atividade eletromiográfica do músculo PM em atletas de halterofilismo (exercício de supino) que foram submetidos a cirurgia esteve dentro dos parâmetros normais para as porções claviculares e esternocostais estudadas.
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Humanos , Músculos Peitorais/lesões , Traumatismos em Atletas , EletromiografiaRESUMO
Abstract Petiveria alliacea L., Phytolaccaceae, a plant used in Afro-Brazilian religious smoke rituals is reported to have "harmonic properties" (anxiolytic effect) by ethnobotanical survey. In the present work, we analyzed the chemical composition of volatiles produced by leaves of P. alliacea, using headspace gas chromatography/mass spectrometry and its potential anxiolytic and toxic effects in smoke-exposed rats. Locomotor activity and anxiety-like behavior were allocated into groups, according to substance administration: acute (locomotor activity) or chronic (anxiety-like behavior) burning charcoal or to smoke from P. alliacea. Inflammatory cell counts in the bronchoalveolar lavage and morphometric analysis in airway were assessed. Animals exposed to P. alliacea smoke had no locomotor activity or elevated plus maze open arm exploration impairment, while lungs had lower number of macrophages in bronchoalveolar fluid and an increased number of mononuclear and polymorphonuclear cells in the peribronchovascular region. Chemical analysis of plant material allowed the identification of dimethylsulfide (18.7%), diethylsulfide (33.4%) and nerolidol (25.8%) as main volatile compounds. Taken together, prolonged exposure to P. alliacea smoke does not induce anxiolytic effects, but histological analyses indicate a possible pulmonary inflammatory response.
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IMPACT, a highly conserved protein, is an inhibitor of the eIF2α kinase GCN2. In mammals, it is preferentially expressed in neurons. Knock-down of IMPACT expression in neuronal cells increases basal GCN2 activation and eIF2α phosphorylation and decreases translation initiation. In the mouse brain, IMPACT is particularly abundant in the hypothalamus. Here we describe that the lack of IMPACT in mice affects hypothalamic functions. Impact-/- mice (Imp-KO) are viable and have no apparent major phenotypic defect. The hypothalamus in these animals shows increased levels of eIF2α phosphorylation, as expected from the described role of IMPACT in inhibiting GCN2 and from its abundance in this brain region. When fed a normal chow, animals lacking IMPACT weight slightly less than wild-type mice. When fed a high-fat diet, Imp-KO animals gain substantially less weight due to lower food intake when compared to wild-type mice. STAT3 signaling was depressed in Imp-KO animals even though leptin levels were identical to the wild-type mice. This finding supports the observation that Imp-KO mice have defective thermoregulation upon fasting. This phenotype was partially dependent on GCN2, whereas the lean phenotype was independent of GCN2. Taken together, our results indicate that IMPACT contributes to GCN2-dependent and -independent mechanisms involved in the regulation of autonomic functions in response to energy availability.
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Regulação da Temperatura Corporal/efeitos dos fármacos , Gorduras na Dieta/efeitos adversos , Hipotálamo/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Obesidade/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Animais , Regulação da Temperatura Corporal/genética , Gorduras na Dieta/farmacologia , Fator de Iniciação 2 em Eucariotos/genética , Fator de Iniciação 2 em Eucariotos/metabolismo , Hipotálamo/patologia , Peptídeos e Proteínas de Sinalização Intracelular/genética , Camundongos , Camundongos Knockout , Obesidade/induzido quimicamente , Obesidade/genética , Obesidade/patologia , Proteínas Serina-Treonina Quinases/genéticaRESUMO
Drug delivery in research on nonhuman animals in the laboratory is still challenging because it is usually invasive and stressful. Stress-free voluntary oral drug administration in water lacks precise control of dose and timing of substance ingestion. Voluntary oral consumption of corticosterone has been previously successfully applied in mice using oat flakes, but protocols for oral corticosterone administration in rats remain unavailable. This study assessed the effectiveness of voluntary oral administration to rats of a palatable piece of bread soaked with corticosterone that can be rapidly prepared and is reliably dose- and timing-controllable. After three familiarization days, all rats ate the bread within 120 seconds of presentation, irrespective of the presence or absence of corticosterone or vehicle. Corticosterone plasma levels remained at basal levels with consumption of vehicle-containing bread, and they were significantly increased with corticosterone-containing bread. Hence, the method enabled corticosterone bodily assimilation while avoiding stress, making it a possible alternative for invasive and stressful procedures. This article includes a methodological refinement that lessens unnecessary discomfort to laboratory animals and is potentially suitable for acute and chronic protocol studies.
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Administração Oral , Corticosterona/administração & dosagem , Autoadministração/métodos , Animais , Pão , Corticosterona/sangue , Masculino , Ratos WistarRESUMO
The present study addressed the effects of sleep deprivation (SD) on AMPA receptor (AMPAR) binding in brain regions associated with learning and memory, and investigated whether treatment with drugs acting on AMPAR could prevent passive avoidance deficits in sleep deprived animals. [(3)H]AMPA binding and GluR1 in situ hybridization signals were quantified in different brain regions of male Wistar rats either immediately after 96 h of sleep deprivation or after 24h of sleep recovery following 96 h of sleep deprivation. Another group of animals were sleep deprived and then treated with either the AMPAR potentiator, aniracetam (25, 50 and 100mg/kg, acute administration) or the AMPAR antagonist GYKI-52466 (5 and 10mg/kg, acute and chronic administration) before passive avoidance training. Task performance was evaluated 2h and 24h after training. A significant reduction in [(3)H]AMPA binding was found in the hippocampal formation of SD animals, while no alterations were observed in GluR1 mRNA levels. The highest dose of aniracetam (100mg/kg) reverted SD-induced impairment of passive avoidance performance in both retention tests, whereas GYKI-52466 treatment had no effect. Pharmacological enhancement of AMPAR function may revert hippocampal-dependent learning impairments produced after SD. We argue that such effects might be associated with reduced AMPAR binding in the hippocampus of sleep deprived animals.
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Aprendizagem da Esquiva/fisiologia , Regulação da Expressão Gênica/fisiologia , Deficiências da Aprendizagem/complicações , Deficiências da Aprendizagem/metabolismo , Receptores de AMPA/metabolismo , Privação do Sono/complicações , Análise de Variância , Animais , Benzodiazepinas/farmacologia , Antagonistas de Aminoácidos Excitatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Masculino , Nootrópicos/farmacologia , Ligação Proteica/efeitos dos fármacos , Pirrolidinonas/farmacologia , Ratos , Ratos Wistar , Receptores de AMPA/genética , Fatores de Tempo , Trítio/metabolismoRESUMO
We investigated the relationship between deficits in fear memory induced by sleep deprivation and pCREB expression in the basal and central nuclei of the amygdala. Sleep deprivation reduced pCREB expression in the central nucleus compared to control or sleep recovered groups, and in the basal nucleus only compared to sleep recovered group. Moreover, 24h of sleep recovery prior to training prevented changes in both pCREB expression and performance.
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Tonsila do Cerebelo/metabolismo , Condicionamento Psicológico/fisiologia , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Medo/fisiologia , Privação do Sono , Animais , Imuno-Histoquímica , Masculino , Memória/fisiologia , Fosforilação , Desempenho Psicomotor/fisiologia , Ratos , Ratos WistarRESUMO
The current study investigated the possible inherent relationship between convulsions and sleep involving the GABA(A)/benzodiazepine site complex. The aim of this study was to determine if rats with high (HTR) and low (LTR) thresholds for clonic convulsions induced by DMCM, a benzodiazepine inverse agonist, differ in the following aspects: (1) sensitivity to the hypnotic effects of the GABA(A) positive allosteric modulators diazepam, pentobarbital and ethanol and (2) in the binding of [(3)H]-flunitrazepam, a benzodiazepine agonist, measured by autoradiography, and [(3)H]-Ro 15-4513, a benzodiazepine partial inverse agonist, to membranes from discrete brain regions. The LTR subgroup presented a shorter diazepam-induced sleeping time compared to that of the HTR subgroup. Biochemical assays revealed that the LTR subgroup did not differ in [(3)H]-flunitrazepam binding compared to the HTR subgroup. With respect to the binding of [(3)H]-Ro 15-4513, the LTR subgroup had higher binding in the brainstem and lower binding in the striatum compared to the HTR subgroup. These results suggest that differences in the benzodiazepine site on the GABA(A) receptor may underlie the susceptibility to DMCM-induced convulsions and sensitivity to the hypnotic effect of diazepam.
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Anticonvulsivantes/uso terapêutico , Azidas/farmacocinética , Benzodiazepinas/farmacocinética , Carbolinas/toxicidade , Convulsivantes/toxicidade , Diazepam/uso terapêutico , Convulsões/tratamento farmacológico , Sono/fisiologia , Animais , Autorradiografia , Limiar Diferencial/efeitos dos fármacos , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Interações Medicamentosas , Etanol/farmacologia , Flunitrazepam/farmacocinética , Moduladores GABAérgicos/farmacologia , Masculino , Pentobarbital/farmacologia , Ratos , Ratos Wistar , Tempo de Reação/efeitos dos fármacos , Convulsões/induzido quimicamente , Convulsões/fisiopatologia , Sono/efeitos dos fármacos , Estatísticas não Paramétricas , Trítio/farmacocinéticaRESUMO
Brain areas expressing c-fos messenger RNA were mapped by quantitative in situ hybridization after 1-2 h of intoxication with 10 µg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, including the supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus, locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NOstimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamic n. failed to induce penile erection, arguing against CNS involvement in this particular effect.
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Encéfalo/efeitos dos fármacos , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurotoxinas/toxicidade , Ereção Peniana/efeitos dos fármacos , Peptídeos/toxicidade , Proteínas Proto-Oncogênicas c-fos/metabolismo , Venenos de Aranha/toxicidade , Animais , Proteínas de Artrópodes/administração & dosagem , Proteínas de Artrópodes/química , Proteínas de Artrópodes/toxicidade , Biomarcadores/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Fármacos do Sistema Nervoso Central/administração & dosagem , Fármacos do Sistema Nervoso Central/toxicidade , Relação Dose-Resposta a Droga , Hibridização In Situ , Injeções Intraventriculares , Masculino , Camundongos , Proteínas do Tecido Nervoso/agonistas , Proteínas do Tecido Nervoso/genética , Neurônios/metabolismo , Neurônios/patologia , Neurotoxinas/administração & dosagem , Neurotoxinas/química , Especificidade de Órgãos , Peptídeos/administração & dosagem , Peptídeos/química , Proteínas Proto-Oncogênicas c-fos/agonistas , Proteínas Proto-Oncogênicas c-fos/genética , RNA Mensageiro/metabolismo , Agonistas de Canais de Sódio , Picada de Aranha/metabolismo , Picada de Aranha/patologia , Venenos de Aranha/administração & dosagem , Venenos de Aranha/químicaRESUMO
Increasing evidence indicates that sleep deprivation alters behavioural responses to various pharmacological agents which might be associated to changes in receptor systems. The present work addressed the effects of sleep deprivation and recovery on behavioural changes induced by MK-801, and investigated whether such effects are related to changes in NMDA receptor (NMDAR) binding. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24 h (SR group). Animals were treated with saline or 0.05, 0.10 or 0.20 mg/kg MK-801 before testing in an open field arena and elevated plus maze. A separate set of animals was sacrificed for [³H]MK-801 binding analysis in 40 brain regions. MK-801-induced hyperlocomotion was facilitated in a dose-dependent fashion after SR, while SD-induced increase in grooming was antagonized by the drug. Anxiolytic effects of 0.05 and 0.10 mg/kg MK-801 were unaffected by SD or SR conditions. No significant differences among groups were found in NMDAR binding. These findings indicate that the combined effects of MK-801 and sleep deprivation and recovery interact in a complex fashion to affect rat behaviour. They further suggest that such effects cannot be attributed to altered NMDAR binding in brain.
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Comportamento Animal/fisiologia , Encéfalo/metabolismo , Maleato de Dizocilpina/farmacologia , Atividade Motora/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , Privação do Sono/metabolismo , Análise de Variância , Animais , Autorradiografia , Comportamento Animal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Masculino , Atividade Motora/efeitos dos fármacos , Ratos , Ratos WistarRESUMO
Brain areas expressing c-fos messenger RNA were mapped by quantitative in situhybridization after 12 h of intoxication with 10 mg/kg Tx2-6, a toxin obtained from the venom of the spider Phoneutria nigriventer. Relative to saline-treated controls, brains from toxin-treated animals showed pronounced c-fos activation in many brain areas, includingthe supraoptic nucleus, the paraventricular nucleus of the hypothalamus, the motor nucleus of the vagus, area postrema, paraventricular and paratenial nuclei of the thalamus,locus coeruleus, central amydaloid nucleus and the bed nucleus of the stria terminalis. The paraventricular hypothalamus and the bed nucleus of the stria terminalis have been implicated in erectile function in other studies. A possible role for central NO is considered. Acute stress also activates many brain areas activated by Tx2-6 as well as with NO stimulated Fos transcription. Brain areas that appear to be selectively activated by Tx2-6, include the paratenial and paraventricular thalamic nuclei, the bed nucleus of the stria terminalis and the area postrema and the dorsal motor n. of vagus in the medulla. However, direct injections of different doses of the toxin into the paraventricular hypothalamicn. failed to induce penile erection, arguing against CNS involvement in thisparticular effect.
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Camundongos , Aranhas/anatomia & histologia , Ereção Peniana , Neurotoxinas/administração & dosagem , Neurotoxinas/análise , Neurotoxinas/intoxicação , Neurotoxinas/toxicidade , Canais de Sódio , Cérebro/anatomia & histologia , Cérebro/fisiopatologia , Priapismo/induzido quimicamenteRESUMO
STUDY OBJECTIVES: Evaluation of modafinil effects on the inhibitory avoidance task (IA). DESIGN: Rats were trained on a multiple trial IA task after receiving modafinil or vehicle injections. In experiment 1 they were trained with a weak protocol under baseline condition and in experiment 2, with a stronger protocol under sleep-deprivation condition. RESULTS: In experiment 1 modafinil improved rats' acquisition whereas the retention test remained unaffected. In Experiment 2 modafinil did not interfere with training performance, but the lower dose prevented the retention impairment in sleep-deprived animals. CONCLUSIONS: Modafinil is able to improve acquisition in normal rats and reverse the long-term memory impairment induced by sleep-deprivation.
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Aprendizagem da Esquiva/efeitos dos fármacos , Compostos Benzidrílicos/farmacologia , Transtornos da Memória/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Privação do Sono/complicações , Análise de Variância , Animais , Comportamento Animal/efeitos dos fármacos , Modelos Animais de Doenças , Masculino , Transtornos da Memória/etiologia , Modafinila , Ratos , Ratos WistarRESUMO
Increasing evidence indicates that sleep deprivation (SD) alters responses to pharmacological agents by affecting specific transmitter systems. The present work addressed deficits in passive avoidance (PA) performance that are seen after SD, and investigated whether treatment with the inverse benzodiazepine agonist beta-CCM could prevent such deficits. Male Wistar rats were deprived of sleep for 96 h using the platform method (SD group), or were sleep deprived and then allowed to recover sleep for 24h (SR group). Animals were treated with saline or 0.5mg/kg beta-CCM before PA training, and were tested 30 min or 24h later. A separate set of animals was sacrificed for [(3)H]Ro 15-4513 binding analysis. beta-CCM increased PA performance in control animals in both short and long term retention tests, whereas SD and SR animals were unaffected by the drug treatment. Interestingly, [(3)H]Ro 15-4513 binding was reduced in the entorhinal cortex in both SD and SR groups. These findings suggest that the lack of promnesic effects of beta-CCM after SD and SR may be associated with benzodiazepine receptor downregulation in specific brain regions related to memory formation.
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Aprendizagem da Esquiva/efeitos dos fármacos , Carbolinas/farmacologia , Antagonistas de Receptores de GABA-A , Privação do Sono , Animais , Autorradiografia , Azidas/farmacologia , Benzodiazepinas/farmacologia , Agonismo Inverso de Drogas , Masculino , Ensaio Radioligante , RatosRESUMO
Accumulating evidence points to the mesolimbic and the nigrostriatal dopamine systems as critical to behavioral sensitization induced by several drugs of abuse. In the present study, we analyzed D1 and D2 binding to brain regions related to these dopaminergic systems during the expression of ethanol-induced behavioral sensitization. The first experiment was performed to demonstrate the effectiveness of the ethanol treatment schedule and challenge used to induce the expression of the behavioral sensitization phenomenon. The second experiment was conducted to study D1 and D2 alterations in several brain regions during the expression of this phenomenon. Mice were ip treated with ethanol or saline for 21 consecutive days and 24 h after the last injection they received an ethanol or a saline challenge injection. Five minutes later, the animals were observed in an open-field for locomotion quantification or were sacrificed and their brains were submitted to autoradiographic binding analyses. No differences among the groups were found for D1 binding levels in all the brain regions analyzed. However, ethanol-sensitized mice showed reduced levels of D2 binding in the olfactory tubercle when compared to the other groups. Our data suggest that D2 receptor changes in the olfactory tubercle seem to play an important role in the expression of ethanol-induced behavioral sensitization.
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Comportamento Animal/efeitos dos fármacos , Depressores do Sistema Nervoso Central/administração & dosagem , Etanol/administração & dosagem , Condutos Olfatórios/metabolismo , Receptores Dopaminérgicos/metabolismo , Análise de Variância , Animais , Autorradiografia/métodos , Benzazepinas/farmacologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Antagonistas de Dopamina/farmacologia , Feminino , Locomoção/efeitos dos fármacos , Camundongos , Condutos Olfatórios/efeitos dos fármacos , Ligação Proteica/efeitos dos fármacos , Racloprida/farmacologia , Receptores Dopaminérgicos/efeitos dos fármacosRESUMO
Rats with unilateral lesion of the substantia nigra pars compacta (SNpc) have been used as a model of Parkinson's disease. Depending on the lesion protocol and on the drug challenge, these rats rotate in opposite directions. The aim of the present study was to propose a model to explain how critical factors determine the direction of these turns. Unilateral lesion of the SNpc was induced with 6-hydroxydopamine (6-OHDA) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Separate analysis showed that neither the type of neurotoxin nor the site of lesion along the nigrostriatal pathway was able to predict the direction of the turns these rats made after they were challenged with apomorphine. However, the combination of these two factors determined the magnitude of the lesion estimated by tyrosine-hydroxylase immunohistochemistry and HPLC-ED measurement of striatal dopamine. Very small lesions did not cause turns, medium-size lesions caused ipsiversive turns, and large lesions caused contraversive turns. Large-size SNpc lesions resulted in an increased binding of [(3)H]raclopride to D2 receptors, while medium-size lesions reduced the binding of [(3)H]SCH-23390 D1 receptors in the ipsilateral striatum. These results are coherent with the model proposing that after challenged with a dopamine receptor agonist, unilaterally SNpc-lesioned rats rotate toward the side with the weaker activation of dopamine receptors. This activation is weaker on the lesioned side in animals with small SNpc lesions due to the loss of dopamine, but stronger in animals with large lesions due to dopamine receptor supersensitivity.
Assuntos
Dopamina/metabolismo , Lateralidade Funcional/fisiologia , Atividade Motora/fisiologia , Transtornos Parkinsonianos/metabolismo , Substância Negra/metabolismo , Análise de Variância , Animais , Apomorfina/farmacologia , Dano Encefálico Crônico/induzido quimicamente , Modelos Animais de Doenças , Agonistas de Dopamina/farmacologia , Lateralidade Funcional/efeitos dos fármacos , Locomoção/efeitos dos fármacos , Locomoção/fisiologia , Intoxicação por MPTP/metabolismo , Intoxicação por MPTP/patologia , Masculino , Atividade Motora/efeitos dos fármacos , Oxidopamina , Transtornos Parkinsonianos/induzido quimicamente , Transtornos Parkinsonianos/patologia , Ratos , Ratos Wistar , Rotação , Índice de Gravidade de Doença , Estatísticas não Paramétricas , Substância Negra/patologiaRESUMO
RATIONALE: Higher doses of benzodiazepines induce sedation. However, in low to moderate doses, benzodiazepines can increase aggressive behavior both after acute and chronic administration. The determinants for increasing aggression after chronic intake of flunitrazepam, a so-called date rape drug, in violence-prone individuals are incompletely understood. OBJECTIVES: The aim of this study is to assess the effects of acute and chronic treatment with flunitrazepam on male aggression in resident rats. We also examined possible changes in binding to benzodiazepine receptors throughout the brain of rats that display aggressive behavior after repeated flunitrazepam treatment using quantitative receptor autoradiography. MATERIALS AND METHODS: The behaviors of the male Wistar resident rats (n = 35) toward a male intruder were recorded for 10 min twice a week. The salient aggressive and non-aggressive elements in the resident rat's behavior were analyzed. Initially, the dose-dependent effects of flunitrazepam (0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) or vehicle were determined in all rats; subsequently, 0.3 mg/kg per day flunitrazepam was administered for 42 days (n = 15), and a parallel group was treated with vehicle (n = 20). After the chronic treatment, the flunitrazepam (0, 0.01, 0.03, 0.1, 0.18, and 0.3 mg/kg) effects were again assessed. RESULTS: The most significant finding is the escalation of aggression after chronic treatment with flunitrazepam. A previously sedative 0.3 mg/kg dose of flunitrazepam engendered very high levels of attack bites, sideways threats, and aggressive postures (total aggression) after 6 weeks of daily administration. Individual differences emerged, and these were associated with decreased binding to benzodiazepine receptors, mainly in the limbic structures such as the cingulate cortex (cingulate areas 1 and 2) and caudate-putamen (posterior part) of aggressive animals, suggesting that these areas are pivotal in the control of emotional and aggressive behavior. CONCLUSIONS: Chronic flunitrazepam produces changes in receptor binding in discrete areas of the cingulate cortex and caudate-putamen that are proposed to be part of the mechanisms for increased expression of aggressive behavior.