RESUMEN
Exposure to alcohol during adolescence impacts cortical and limbic brain regions undergoing maturation. In rodent models, long-term effects on behavior and neurophysiology have been described after adolescent intermittent ethanol (AIE), especially in males. We hypothesized that AIE in female rats increases conditional approach to a reward-predictive cue and corresponding neuronal activity in the orbitofrontal cortex (OFC) and nucleus accumbens (NAc). We evaluated behavior and neuronal firing after AIE (5 g/kg intragastric) or water (CON) in adult female rats. Both AIE and CON groups expressed a ST phenotype, and AIE marginally increased sign-tracking (ST) and decreased goal-tracking (GT) metrics. NAc neurons exhibited phasic firing patterns to the conditional stimulus (CS), with no differences between groups. In contrast, neuronal firing in the OFC of AIE animals was greater at CS onset and offset than in CON animals. During reward omission, OFC responses to CS offset normalized to CON levels, but enhanced OFC firing to CS onset persisted in AIE. We suggest that the enhanced OFC neural activity observed in AIE rats to the CS could contribute to behavioral inflexibility. Ultimately, AIE persistently impacts the neurocircuitry of reward-motivated behavior in female rats.
Asunto(s)
Etanol , Núcleo Accumbens , Corteza Prefrontal , Recompensa , Animales , Femenino , Corteza Prefrontal/fisiología , Corteza Prefrontal/efectos de los fármacos , Ratas , Etanol/farmacología , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/fisiología , Neuronas/fisiología , Neuronas/efectos de los fármacos , Condicionamiento Clásico/efectos de los fármacos , Conducta Animal/efectos de los fármacos , Señales (Psicología) , Ratas Sprague-DawleyRESUMEN
Persistent pain conditions and sleep disorders are public health problems worldwide. It is widely accepted that sleep disruption increases pain sensitivity; however, the underlying mechanisms are poorly understood. In this study, we used a protocol of 6 hours a day of total sleep deprivation for 3 days in rats to advance the understanding of these mechanisms. We focused on gender differences and the dopaminergic mesocorticolimbic system. The findings demonstrated that sleep restriction (SR) increased pain sensitivity in a similar way in males and females, without inducing a significant stress response. This pronociceptive effect depends on a nucleus accumbens (NAc) neuronal ensemble recruited during SR and on the integrity of the anterior cingulate cortex (ACC). Data on indirect dopaminergic parameters, dopamine transporter glycosylation, and dopamine and cyclic adenosine monophosphate (AMP)-regulated phosphoprotein-32 phosphorylation, as well as dopamine, serotonin, and norepinephrine levels, suggest that dopaminergic function decreases in the NAc and ACC after SR. Complementarily, pharmacological activation of dopamine D2, but not D1 receptors either in the ACC or in the NAc prevents SR from increasing pain sensitivity. The ACC and NAc are the main targets of dopaminergic mesocorticolimbic projections with a key role in pain modulation. This study showed their integrative role in the pronociceptive effect of SR, pointing to dopamine D2 receptors as a potential target for pain management in patients with sleep disorders. These findings narrow the focus of future studies on the mechanisms by which sleep impairment increases pain sensitivity. PERSPECTIVE: This study demonstrates that the pronociceptive effect of SR affects similarly males and females and depends on a NAc neuronal ensemble recruited during SR and on the integrity of the ACC. Findings on dopaminergic function support dopamine D2 receptors as targets for pain management in sleep disorders patients.
Asunto(s)
Dopamina , Núcleo Accumbens , Humanos , Masculino , Ratas , Animales , Núcleo Accumbens/fisiología , Dopamina/farmacología , Giro del Cíngulo , Dolor , Privación de Sueño/complicacionesRESUMEN
Ultrasonic vocalizations (USV) are emitted by both young pups and adult rats to convey positive or negative emotional states. These USV manifestations are contingent on factors including developmental stage, situational requirements, and individual dispositions. Pups emit 40-kHz USV when separated from their mother and litter, which function to elicit maternal care. Conversely, adult rats can produce 50-kHz USV in response to stimuli that elicit reward-related states, including natural rewards, stimulant drugs, and reward-predictive stimuli. The present study aims to investigate whether pup 40-kHz USV can serve as predictors of behaviors related to positive or negative states in adult rats. Both male and female Wistar pups were initially tested on the 11th postnatal day and subsequently in adulthood. There was no significant difference in the number of 40-kHz ultrasonic vocalizations between male and female pups. However, cocaine elicited more 50-kHz USV and hyperactivity in adult females compared to males. Notably, cocaine increased the proportion of step and trill USV subtypes in both adult males and females. Interestingly, this effect of cocaine was stronger in females that were in the diestrus, compared to the estrus phase. In males, a significant positive correlation was found between pup 40-kHz USV and lower anxiety scores in adult male but not female rats tested on the elevated plus-maze test. Furthermore, no significant correlation was found between pup 40-kHz and adult 50-kHz USV in both males and females, whether in undrugged (saline) or in cocaine-treated rats. It is possible that the 40-kHz USV emitted by pups predicted reduced anxiety-like behavior only for male rats because they could elicit maternal care directed specifically to male pups. These findings suggest that 40-kHz USV can serve as an indicator of the emotional link between the rat mother and male pups. Indeed, this suggests that maternal care exerts a positive influence on the emotional state during adulthood.
Asunto(s)
Cocaína , Ultrasonido , Ratas , Animales , Femenino , Masculino , Vocalización Animal/fisiología , Ratas Wistar , Cocaína/farmacología , Prueba de Laberinto ElevadoRESUMEN
Cocaine use disorder (CUD) is a worldwide public health problem, associated with severe psychosocial and economic impacts. Currently, no FDA-approved treatment is available for CUD. However, an emerging body of evidence from clinical and preclinical studies suggests that biperiden, an M1 muscarinic receptor antagonist, presents potential therapeutic use for CUD. These studies have suggested that biperiden may reduce the reinforcing effects of cocaine. It is well established that rodents emit 50-kHz ultrasonic vocalizations (USV) in response to natural rewards and stimulant drugs, including cocaine. Nonetheless, the effects of biperiden on the cocaine-induced increase of 50-kHz USV remains unknown. Here, we hypothesized that biperiden could antagonize the acute effects of cocaine administration on rat 50-kHz USV. To test this hypothesis, adult male Wistar rats were divided into four experimental groups: saline, 5 mg/kg biperiden, 10 mg/kg cocaine, and biperiden/cocaine (5 and 10 mg/kg, i.p., respectively). USV and locomotor activity were recorded in baseline and test sessions. As expected, cocaine administration significantly increased the number of 50-kHz USV. Biperiden administration effectively antagonized the increase in 50-kHz USV induced by cocaine. Cocaine administration also increased the emission of trill and mixed 50 kHz USV subtypes and this effect was antagonized by biperiden. Additionally, we showed that biperiden did not affect the cocaine-induced increase in locomotor activity, although biperiden administration per se increased locomotor activity. In conclusion, our findings indicate that administering biperiden acutely reduces the positive affective effects of cocaine, as demonstrated by its ability to inhibit the increase in 50-kHz USV.
Asunto(s)
Cocaína , Ultrasonido , Ratas , Masculino , Animales , Ratas Wistar , Biperideno/farmacología , Vocalización Animal/fisiología , Cocaína/farmacología , LocomociónRESUMEN
Methylphenidate is a stimulant used to treat attention deficit and hyperactivity disorder (ADHD). In the last decade, illicit use of methylphenidate has increased among healthy young adults, who consume the drug under the assumption that it will improve cognitive performance. However, the studies that aimed to assess the methylphenidate effects on memory are not consistent. Here, we tested whether the effect of methylphenidate on a spatial memory task can be explained as a motivational and/or a reward effect. We tested the effects of acute and chronic i.p. administration of 0.3, 1 or 3 mg/kg of methylphenidate on motivation, learning and memory by using the 8-arm radial maze task. Adult male Wistar rats learned that 3 of the 8 arms of the maze were consistently baited with 1, 3, or 6 sucrose pellets, and the number of entries and reentries into reinforced and non-reinforced arms of the maze were scored. Neither acute nor chronic (20 days) methylphenidate treatment affected the number of entries in the non-baited arms. However, chronic, but not acute, 1-3 mg/kg methylphenidate increased the number of reentries in the higher reward arms, which suggests a motivational/rewarding effect rather than a working memory deficit. In agreement with this hypothesis, the methylphenidate treatment also decreased the approach latency to the higher reward arms, increased the approach latency to the low reward arm, and increased the time spent in the high, but not low, reward arm. These findings suggest that methylphenidate may act more as a motivational enhancer rather than a cognitive enhancer in healthy people.
Asunto(s)
Trastorno por Déficit de Atención con Hiperactividad , Estimulantes del Sistema Nervioso Central , Metilfenidato , Animales , Ratas , Masculino , Metilfenidato/farmacología , Metilfenidato/uso terapéutico , Motivación , Ratas Wistar , Estimulantes del Sistema Nervioso Central/farmacología , Estimulantes del Sistema Nervioso Central/uso terapéutico , Recompensa , Trastorno por Déficit de Atención con Hiperactividad/tratamiento farmacológicoRESUMEN
Parkinson's disease is a neurodegenerative disease, the etiology of which remains unknown, but some likely causes include oxidative stress, mitochondrial dysfunction and neuroinflammation. Peroxisome-proliferator-activated receptor (PPAR) agonists have been studied in animal models of Parkinson's disease and have shown neuroprotective effects. In this study, we aimed to (1) confirm the neuroprotective effects of PPAR-alpha agonist fenofibrate. To this end, male rats received fenofibrate (100 mg/kg) orally for 15 days, 5 days before the intraperitoneal injections of rotenone (2.5 mg/kg for 10 days). After finishing the treatment with rotenone and fenofibrate, animals were subjected to the open field, the forced swim test and the two-way active avoidance task. Subsequently, rats were euthanized for measurement of dopamine and metabolites levels in the striatum and quantification of tyrosine hydroxylase-immunoreactive neurons in the substantia nigra pars compacta (SNpc). In addition, we aimed to (2) evaluate the neuroprotective effects of fenofibrate on the accumulation of α-synuclein aggregates. Here, rats were treated for 5 days with fenofibrate continuing for over 28 days with rotenone. Then, animals were perfused for immunohistochemistry analysis of α-synuclein. The results showed that fenofibrate reduced depressive-like behavior and memory impairment induced by rotenone. Moreover, fenofibrate diminished the depletion of striatal dopamine and protected against dopaminergic neuronal death in the SNpc. Likewise, the administration of fenofibrate attenuated the aggregation of α-synuclein in the SNpc and striatum in the rotenone-lesioned rats. Our study confirmed that fenofibrate exerted neuroprotective effects because parkinsonian rats exhibited reduced behavioral, neurochemical and immunohistochemical changes, and importantly, a lower number of α-synuclein aggregates.
Asunto(s)
Fenofibrato , Enfermedades Neurodegenerativas , Fármacos Neuroprotectores , Enfermedad de Parkinson , Masculino , Ratas , Animales , Rotenona/farmacología , Enfermedad de Parkinson/metabolismo , Fenofibrato/farmacología , alfa-Sinucleína , Neuroprotección , Fármacos Neuroprotectores/farmacología , Dopamina/metabolismo , Receptores Activados del Proliferador del Peroxisoma/metabolismo , Receptores Activados del Proliferador del Peroxisoma/farmacología , Modelos Animales de Enfermedad , Neuronas Dopaminérgicas , Sustancia NegraRESUMEN
BACKGROUND AND PURPOSE: Currently, there is no effective drug to treat cocaine-use disorder, which affects millions of people worldwide. Benzodiazepines are potential therapeutic candidates, as microdialysis and voltammetry studies have shown that they can decrease dopamine concentrations in the nucleus accumbens of rodents and block the increase in dopamine levels and appetitive 50-kHz ultrasonic vocalizations (USVs) induced by amphetamine in rats. EXPERIMENTAL APPROACH: Here, we tested whether administration of 2.5-mg·kg-1 diazepam (i.p.) in adult male rats could block the effects of 20-mg·kg-1 cocaine (i.p.) on electrically evoked phasic dopamine signals in the nucleus accumbens measured by fast-scan cyclic voltammetry, as well as 50-kHz USV and locomotor activity. KEY RESULTS: Cocaine injection increased evoked dopamine signals up to threefold within 5 min, and the increase was significantly higher than baseline for at least 75 min. The injection of diazepam, 5 min after cocaine, attenuated the cocaine effect by nearly 50%, and this attenuation was maintained for at least 40 min. Behaviourally, cocaine increased the number of appetitive 50-kHz calls by about 12-fold. Diazepam significantly blocked this effect for the entire duration of the session. Also, cocaine-treated rats were more active than controls and diazepam significantly attenuated cocaine-induced locomotion, by up to 50%. CONCLUSION AND IMPLICATIONS: These results suggest that the neurochemical and psychostimulant effects of cocaine can be mitigated by diazepam. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.
Asunto(s)
Cocaína , Dopamina , Animales , Cocaína/farmacología , Diazepam/farmacología , Dopamina/farmacología , Humanos , Locomoción , Masculino , Núcleo Accumbens , Ratas , Ultrasonido , Vocalización AnimalRESUMEN
BACKGROUND: Infection after cardiovascular surgery is multifactorial. We sought to determine whether the anthropometric profile influences the occurrence of infection after isolated coronary artery bypass grafting (CABG). METHODS: Between January 2011 and June 2016, 1777 consecutive adult patients were submitted to isolated coronary artery bypass grafting. Mean age was 61.7 ± 9.8 years and 1193 (67.1%) were males. Patients were divided into four groups according to the body mass index (BMI) classification: underweight (BMI < 18.5 kg/m2 ; N = 17, 0.9%), normal range (BMI: 18.5-24.99 kg/m2 ; N = 522, 29.4%), overweight (BMI: 25-29.99 kg/m2 ; N = 796, 44.8%), and obese (BMI > 30 kg/m2 ; N = 430, 24.2%). In-hospital outcomes were compared and independent predictors of infection were obtained through multiple Poisson regression with a robust variation. RESULTS: Independent predictors of any infection morbidity were female sex (relative ratio [RR], 1.47; p = .002), age > 60 years (RR, 1.85; p < .0001), cardiopulmonary bypass > 120 min (RR, 1.89; p = .0007), preoperative myocardial infarction < 30 days (RR, 1.37; p = .01), diabetes mellitus (RR, 1.59; p = .0003), ejection fraction < 48% (RR, 2.12; p < .0001), and blood transfusion (RR, 1.55; p = .0008). Among other variables, obesity, as well as diabetes mellitus, were independent predictors of superficial and deep sternal wound infection. CONCLUSIONS: Other factors rather than the anthropometric profile are more important in determining the occurrence of any infection after CABG. However, surgical site infection has occurred more frequently in obese patients. Appropriate patient selection, control of modifiable factors, and application of surgical bundles would minimize this important complication.
Asunto(s)
Puente de Arteria Coronaria , Delgadez , Adulto , Anciano , Índice de Masa Corporal , Femenino , Humanos , Masculino , Persona de Mediana Edad , Morbilidad , Estudios Retrospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
INTRODUCTION: Cardiovascular diseases are the main cause of mortality worldwide, and systemic arterial hypertension is associated with a large number of these cases. The objective of health professionals and health policies should be searching for the best therapeutics to control this disease. A recent consensus indicated that ß-blockers have recently lost their place in initial indications for the treatment of systemic arterial hypertension and are now more indicated for the treatment of hypertension in association with other clinical situations such as angina, heart failure and arrhythmia; however, it is known that this approach was based on studies that evaluated older ß-blockers such as atenolol. OBJECTIVE: The main objective of this study was to perform a systematic review with subsequent meta-analysis on the use of nebivolol for hypertensive disease treatment, comparing it with drugs of the main antihypertensive classes. METHODS: This systematic review was based on a search of the MEDLINE (via Pubmed), Scopus, Cochrane, International Pharmaceuticals Abstracts (IPA), and Lilacs databases for randomized and double-blind clinical trials. In addition, we also searched for gray literature studies, to 31 July 2015. Next, a cumulative meta-analysis was performed, with studies being added in a sequential manner, evaluating their impact on the combined effect. For this project, we only meta-analyzed direct comparisons of random effect. RESULTS: Overall, 981 clinical trials were included in this systematic review. After careful analysis, 34 randomized and double-blind clinical trials were included to investigate the efficacy of nebivolol on systolic (SBP) and diastolic blood pressure (DBP) control and adverse effects. The study population comprised 12,465 patients with systemic arterial hypertension (SAH) aged between 18 and 85 years; 17% of subjects were of Black ethnicity, approximately 55% were men, and almost 10% had diabetes. In SBP management, nebivolol was superior to other ß-blockers and diuretics and showed no difference in efficacy when compared with angiotensin receptor blockers or calcium channel blockers. There were insufficient studies on angiotensin-converting enzyme inhibitors for adequate comparison of both SBP and DBP control. For DBP control, nebivolol was more efficient than other ß-blockers, angiotensin receptor blockers, diuretics, and calcium channel blockers. DISCUSSION: Nebivolol is a third-generation ß-blocker with additional capabilities to improve blood pressure levels in patients with arterial hypertension, because it acts by additional mechanisms such as endothelium-dependent vasodilation associated with L-arginine and oxide nitric acid, nitric oxide activity on smooth muscle cells, decreasing platelet aggregation, and leukocyte adhesion in the endothelium, decreasing oxidative stress. Although nebivolol has shown good results in controlling hypertension in this study (with few adverse events when compared with placebo treatment) and has an unquestionable benefit in individuals with heart failure (mainly with reduced ejection fraction), there is a lack of studies proving the benefit of this drug for controlling hypertension and reducing clinical outcomes such as cardiovascular (or general) mortality, acute myocardial infarction, or stroke. CONCLUSIONS: Nebivolol demonstrated at least similar control of blood pressure levels in hypertensive individuals when compared with drugs of the most used classes. In addition, in relation to the control of arterial hypertension, studies with clinical outcomes should be performed to ensure the use of this drug in detriment to others with these well-established results.
Asunto(s)
Antihipertensivos/uso terapéutico , Hipertensión/tratamiento farmacológico , Nebivolol/uso terapéutico , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Inhibidores de la Enzima Convertidora de Angiotensina/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Diabetes Mellitus/epidemiología , Diuréticos/uso terapéutico , Método Doble Ciego , Quimioterapia Combinada , Femenino , Humanos , Hipertensión/epidemiología , Masculino , Persona de Mediana Edad , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores Sexuales , Factores Socioeconómicos , Adulto JovenRESUMEN
The most common features of Parkinson's disease (PD) are motor impairments, but many patients also present depression and memory impairment. Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, has been shown to be effective in patients with treatment-resistant major depression. Thus, the present study evaluated the action of ketamine on memory impairment and depressive-like behavior in an animal model of PD. Male Wistar rats received a bilateral infusion of 6 µg/side 6-hydroxydopamine (6-OHDA) into the substantia nigra pars compacta (SNc). Short-term memory was evaluated by the social recognition test, and depressive-like behaviors were evaluated by the sucrose preference and forced swimming tests (FST). Drug treatments included vehicle (i.p., once a week); ketamine (5, 10 and 15 mg/kg, i.p., once a week); and imipramine (20 mg/kg, i.p., daily). The treatments were administered 21 days after the SNc lesion and lasted for 28 days. The SNc lesion impaired short-term social memory, and all ketamine doses reversed the memory impairment and anhedonia (reduction of sucrose preference) induced by 6-OHDA. In the FST, 6-OHDA increased immobility, and all doses of ketamine and imipramine reversed this effect. The anti-immobility effect of ketamine was associated with an increase in swimming but not in climbing, suggesting a serotonergic effect. Ketamine and imipramine did not reverse the 6-OHDA-induced reduction in tyrosine hydroxylase immunohistochemistry in the SNc. In conclusion, ketamine reversed depressive-like behaviors and short-term memory impairment in rats with SNc bilateral lesions, indicating a promising profile for its use in PD patients.
Asunto(s)
Conducta Animal/efectos de los fármacos , Ketamina/farmacología , Memoria a Corto Plazo/efectos de los fármacos , Enfermedad de Parkinson/tratamiento farmacológico , Animales , Depresión/tratamiento farmacológico , Depresión/patología , Modelos Animales de Enfermedad , Imipramina/farmacología , Masculino , Oxidopamina/farmacología , Porción Compacta de la Sustancia Negra/efectos de los fármacos , Ratas Wistar , Receptores de N-Metil-D-Aspartato/efectos de los fármacosRESUMEN
Activation of midbrain dopamine neurons in response to positive prediction errors and reward predictive cues is proposed to "energize" reward seeking behaviors and approach responses to places where the reward is expected. In the present study, we tested the effect of the D2-dopamine receptor antagonist haloperidol on response latencies to enter two arms of a Y-maze with different reward probabilities. Adult male Wistar rats were trained to explore the Y-maze with sucrose pellets placed 30% of times at the end of one arm and 70% of times at the opposite arm. Therefore, the reward expectation was different among arms, and was updated in the trials when the reward was omitted. After training, rats received 0.05, 0.10, 0.15 mg/kg haloperidol, or saline 30 min before the test session. In the last, but not in the first trials, haloperidol caused a dose-dependent increase in arm choice latency and response latency. Saline, but not haloperidol, treated rats presented significantly longer response latencies for the 30% compared to the 70% reward probability arm. Haloperidol also caused a dose-dependent decrease in the number of entries in the 70% reward probability arm, increased the number of non-responses, and caused a dose-dependent increase in the number of re-entries in the 30% reward probability arm after non-rewarded trials. Control experiments suggested that haloperidol did not cause motor impairment or satiation, but rather impaired learning and motivation scores by reducing the reward expectation.
Asunto(s)
Haloperidol/efectos adversos , Aprendizaje/efectos de los fármacos , Motivación/efectos de los fármacos , Animales , Señales (Psicología) , Dopamina/farmacología , Antagonistas de Dopamina/farmacología , Antagonistas de los Receptores de Dopamina D2/farmacología , Haloperidol/farmacología , Aprendizaje/fisiología , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Modelos Estadísticos , Motivación/fisiología , Aprendizaje por Probabilidad , Ratas , Ratas Wistar , RecompensaRESUMEN
BACKGROUND AND AIM OF THE STUDY: In developed countries, the shortage of viable donors is the main limiting factor of heart transplantation. The aim of this study is to determine whether the same reality applies to Brazil. METHODS: Between January 2012 and December 2014, 299 adult heart donor offers were studied in terms of donor profiles and reasons for refusal. The European donor scoring system was calculated, being high-risk donors defined as more than 17 points. The donor scoring system was used to objectively determine the donor profile and correlate with donor acceptance and posttransplant primary graft dysfunction and recipient survival. Cox proportional hazard model was used in determining the predictors of long-term mortality. RESULTS: The rates of donor acceptance and heart transplants performed were 45.8% and 19.3%, respectively. Reasons for refusal were mostly nonmedical (53.7%). The majority of donors were classified as high-risk (65.5%). Hearts from high-risk donors did not impact primary graft dysfunction (14.3% vs 10%; P = .6), neither long-term survival (P = .4 by logrank test). Recipient's age was greater than 50 years (hazard ratio, 6.02; 95% confidence interval, 2.41-16.08; P < .0001) and was the only predictor of long-term mortality. CONCLUSIONS: The shortage of donors is not the main limiting factor of heart transplantation in the Mid-West of Brazil. Nonmedical issues represent the main reason for organ discard. Most of the donors are classified as high risk which indicates that an expanded donor pool is a routine practice in our region, and donor scoring does not seem to influence to proceed with the transplant.
Asunto(s)
Trasplante de Corazón , Donantes de Tejidos/provisión & distribución , Brasil/epidemiología , HumanosRESUMEN
BACKGROUND AND AIM: Complications of inferior vena cava filters are relatively common, and they vary according to different filter types and designs. We aim to present a case of penetrated inferior vena cava filter into the liver. METHODS: Case report. RESULTS: A 42-year old man with thrombophilia (prothrombin gene mutation) required the insertion of an inferior vena cava filter because of recurrent gastrointestinal bleeding associated with oral anticoagulation. However, it penetrated through the retro-hepatic vena cava into the liver, being manifested by constant, blunt abdominal pain. Endovascular retrieval was considered of extreme risk, though a surgical approach was performed under cardiopulmonary bypass with deep hypothermic circulatory arrest. The patient has recovered uneventfully with complete symptom relief. CONCLUSIONS: In symptomatic penetrated vena cava filters in which endovascular retrieval is not feasible, a surgical approach with appropriate planning is a safe and effective treatment.
Asunto(s)
Paro Circulatorio Inducido por Hipotermia Profunda/métodos , Remoción de Dispositivos/métodos , Hígado/lesiones , Hígado/cirugía , Falla de Prótesis , Filtros de Vena Cava/efectos adversos , Vena Cava Inferior/cirugía , Adulto , Puente Cardiopulmonar , Procedimientos Endovasculares/métodos , Humanos , Hígado/irrigación sanguínea , Masculino , Resultado del TratamientoRESUMEN
Anxiety in Parkinson's disease may represent a physiological reaction to the development of other symptoms during disease progression. However, evidence suggests that the incidence of anxiety disorders in Parkinson's disease may be related to neurochemical changes. The present study addresses the question whether dopamine, noradrenaline and serotonin levels in brain structures related to Parkinson's disease and anxiety are responsible for anxiety-like behavior by using an animal model of parkinsonism based in the bilateral injection of the neurotoxin 6-hydroxydopamine (6-OHDA) in the substantia nigra pars compacta. For this, one day after the injection of 6-OHDA, the animals exhibited hypolocomotion and a lower frequency of rearings in the open field test, which was spontaneously reversed on the last day of motor assessment (day 21). The 6-OHDA injection also induced anxiety-like behavior in the elevated plus maze and contextual fear conditioning test (day 21 and 24, respectively). Neurochemical analysis showed a reduction of dopamine and norepinephrine levels in the striatum, prefrontal cortex, and amygdala. In addition, while the serotonin levels were reduced in the striatum and prefrontal cortex, it was increased in the amygdala. The present study indicates that the model of 6-OHDA-induced parkinsonism in rats induced an anxiety-like behavior that may be related to a dysregulation of neurotransmitter systems in brain areas involved with anxiety such as the amygdala, prefrontal cortex and striatum.
Asunto(s)
Ansiedad/metabolismo , Neurotransmisores/metabolismo , Oxidopamina/farmacología , Adrenérgicos , Amígdala del Cerebelo/metabolismo , Animales , Trastornos de Ansiedad/metabolismo , Conducta Animal , Encéfalo/metabolismo , Cuerpo Estriado/metabolismo , Modelos Animales de Enfermedad , Dopamina/metabolismo , Masculino , Norepinefrina/metabolismo , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Corteza Prefrontal/metabolismo , Ratas , Ratas Wistar , Serotonina/metabolismo , Sustancia Negra/metabolismoRESUMEN
BACKGROUND: Conditioned stimuli (CS) that predict reward delivery acquire the ability to induce phasic dopamine release in the nucleus accumbens (NAc). This dopamine release may facilitate conditioned approach behavior, which often manifests as approach to the site of reward delivery (called "goal-tracking") or to the CS itself (called "sign-tracking"). Previous research has linked sign-tracking in particular to impulsivity and drug self-administration, and addictive drugs may promote the expression of sign-tracking. Ethanol (EtOH) acutely promotes phasic release of dopamine in the accumbens, but it is unknown whether an alcoholic reward alters dopamine release to a CS. We hypothesized that Pavlovian conditioning with an alcoholic reward would increase dopamine release triggered by the CS and subsequent sign-tracking behavior. Moreover, we predicted that chronic intermittent EtOH (CIE) exposure would promote sign-tracking while acute administration of naltrexone (NTX) would reduce it. METHODS: Rats received 14 doses of EtOH (3 to 5 g/kg, intragastric) or water followed by 6 days of Pavlovian conditioning training. Rewards were a chocolate solution with or without 10% (w/v) alcohol. We used fast-scan cyclic voltammetry to measure phasic dopamine release in the NAc core in response to the CS and the rewards. We also determined the effect of NTX (1 mg/kg, subcutaneous) on conditioned approach. RESULTS: Both CIE and alcoholic reward, individually but not together, associated with greater dopamine to the CS than control conditions. However, this increase in dopamine release was not linked to greater sign-tracking, as both CIE and alcoholic reward shifted conditioned approach from sign-tracking behavior to goal-tracking behavior. However, they both also increased sensitivity to NTX, which reduced goal-tracking behavior. CONCLUSIONS: While a history of EtOH exposure or alcoholic reward enhanced dopamine release to a CS, they did not promote sign-tracking under the current conditions. These findings are consistent with the interpretation that EtOH can stimulate conditioned approach, but indicate that the conditioned response may manifest as goal-tracking.
Asunto(s)
Condicionamiento Clásico/efectos de los fármacos , Dopamina/metabolismo , Etanol/farmacología , Núcleo Accumbens/efectos de los fármacos , Núcleo Accumbens/metabolismo , Recompensa , Animales , Señales (Psicología) , Técnicas Electroquímicas , Etanol/antagonistas & inhibidores , Masculino , Naltrexona/farmacología , RatasRESUMEN
RATIONALE: We have recently shown that the benzodiazepine diazepam inhibits dopamine release in the NAc and blocks the increased release of dopamine induced by DL-amphetamine. Rewarding stimuli and many drugs of abuse can induce dopamine release in the nucleus accumbens as well as 50-kHz ultrasonic vocalizations (USVs) in rats. OBJECTIVES: In the present study, we tested the hypothesis that diazepam can also block the increase in locomotor activity and USVs elicited by amphetamine. METHODS: Fifty-kilohertz USVs, stereotypy, and locomotor behavior were scored in adult male Wistar rats treated with i.p. injections of saline, 3 mg/kg DL-amphetamine, 2 mg/kg diazepam, 0.2 mg/kg haloperidol, or a combination of these drugs. RESULTS: In agreement with previous studies, amphetamine caused significant increases in the number of USV calls, stereotypies, and locomotor activity. The D2 dopamine receptor antagonist haloperidol blocked the effects of amphetamine on USVs, stereotypy, and locomotor activity. Diazepam blocked the effect of amphetamine on USV and stereotypy, but not on horizontal locomotion. CONCLUSIONS: These results suggest that diazepam blocks the rewarding effect of amphetamine. This finding is promising for basic research regarding treatments of substance use disorders and evaluation of the impact of benzodiazepines on motivation.
Asunto(s)
Anfetamina/farmacología , Diazepam/farmacología , Locomoción/efectos de los fármacos , Conducta Estereotipada/efectos de los fármacos , Ondas Ultrasónicas , Vocalización Animal/efectos de los fármacos , Anfetamina/antagonistas & inhibidores , Animales , Dopamina/farmacología , Dopaminérgicos/farmacología , Moduladores del GABA/farmacología , Locomoción/fisiología , Masculino , Motivación/efectos de los fármacos , Motivación/fisiología , Núcleo Accumbens/efectos de los fármacos , Ratas , Ratas Wistar , Receptores de Dopamina D1/antagonistas & inhibidores , Conducta Estereotipada/fisiología , Vocalización Animal/fisiologíaRESUMEN
INTRODUCTION: Early detection of left ventricular systolic dysfunction (LVSD) is important for therapeutic strategies for Duchenne muscular dystrophy (DMD) patients. We analyzed myocardial strain using echocardiography for early detection of LVSD and determined the predictors of early LVSD. METHODS: This investigation was a cross-sectional study of 40 DMD patients with normal left ventricular ejection fraction. Global longitudinal strain (GLS) was used to analyze subtle disturbances in longitudinal contraction of the myocardium. Patients were determined to have early LVSD (GLS > -18) or normal left ventricular systolic function (GLS ≤ -18). RESULTS: Patients who had early LVSD were older and had a higher frequency of corticosteroid therapy and of mutations in exons 45, 46, 47, 48, 49, 50, and 52. DISCUSSION: Myocardial strain measurements are useful for the early diagnosis of LVSD in DMD patients. Older age, use of corticosteroids, and mutations within the "hot-spot" region of the DMD gene are associated with early LVSD. Muscle Nerve, 2018.
RESUMEN
Midbrain dopamine neurons play critical roles in reward- and aversion-driven associative learning. However, it is not clear whether they do this by a common mechanism or by separate mechanisms that can be dissociated. In the present study we addressed this question by testing whether a partial lesion of the dopamine neurons of the rat SNc has comparable effects on conditioned place preference (CPP) learning and conditioned place aversion (CPA) learning. Partial lesions of dopamine neurons in the rat substantia nigra pars compacta (SNc) induced by bilateral intranigral infusion of 6-hydroxydopamine (6-OHDA, 3µg/side) or 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP, 200µg/side) impaired learning of conditioned place aversion (CPA) without affecting conditioned place preference (CPP) learning. Control experiments demonstrated that these lesions did not impair motor performance and did not alter the hedonic value of the sucrose and quinine. The number of dopamine neurons in the caudal part of the SNc positively correlated with the CPP scores of the 6-OHDA rats and negatively correlated with CPA scores of the SHAM rats. In addition, the CPA scores of the 6-OHDA rats positively correlated with the tissue content of striatal dopamine. Insomuch as reward-driven learning depends on an increase in dopamine release by nigral neurons, these findings show that this mechanism is functional even in rats with a partial lesion of the SNc. On the other hand, if aversion-driven learning depends on a reduction of extracellular dopamine in the striatum, the present study suggests that this mechanism is no longer functional after the partial SNc lesion.