RESUMEN
Bechara (2003) describes a model for disturbances in executive functions related to addiction. This model involves deficits in decision-making and in suppressing pre-potent representations or response patterns. We tested this model in 29 individuals with long-term heavy alcohol dependency and compared their performance with that of 20 control subjects. Only individuals without memory impairment, with normal intelligence and normal visual response times were included. We examined word fluency, object alternation, spatial stimulus-response incompatibility, extra-dimensional shift learning and decision-making using the Gambling task. We subtracted the performance in a control condition from that of the executive condition, in order to focus specifically on the executive component of each task. Only the object alternation and incompatibility tasks revealed significant differences between the group of alcoholics and the control group. Moreover, response times in the object alternation task correlated with duration of alcohol dependency. The results do not argue in favor of a specific deficit in decision-making or in shifting between relevant representations. We conclude that long-term alcohol abuse leads to an impairment in conditional responding, provided the response depends on former reactions or the inhibition of pre-potent response patterns.
Asunto(s)
Alcoholismo/complicaciones , Trastornos del Conocimiento/diagnóstico , Toma de Decisiones/fisiología , Tiempo de Reacción/fisiología , Conducta Verbal/fisiología , Adulto , Alcoholismo/psicología , Cognición/fisiología , Trastornos del Conocimiento/fisiopatología , Condicionamiento Psicológico , Aprendizaje Discriminativo/fisiología , Femenino , Juegos Experimentales , Humanos , Masculino , Persona de Mediana Edad , Modelos Neurológicos , Inhibición Neural/fisiología , Pruebas Neuropsicológicas , Factores de TiempoRESUMEN
The effect of long-term heavy alcohol consumption on brain functions is still under debate. The authors investigated a sample of 17 Korsakoff amnesics, 23 alcoholics without Korsakoff's syndrome, and 21 controls with peripheral nerve diseases, matched for intelligence and education. Executive functions were examined for word fluency, the modified Wisconsin Card Sorting Test, an alternate response task, and an "n-back" working memory task. Korsakoff amnesics, but not alcoholics, showed a marked memory impairment. They also scored lower in each of the executive tasks-the alcoholics only in the alternate response task. This task also correlated with the years of the alcohol dependency. First, the authors conclude that Korsakoff's syndrome is associated not only with a memory impairment but also with a global executive deficit. Second, the decline in the ability to alternate between different responses argues for a restricted neurotoxic effect of alcohol on some frontal lobe areas.
Asunto(s)
Alcoholismo/psicología , Lóbulo Frontal/fisiopatología , Síndrome de Korsakoff/psicología , Desempeño Psicomotor , Adulto , Anciano , Alcoholismo/fisiopatología , Estudios de Casos y Controles , Femenino , Humanos , Síndrome de Korsakoff/fisiopatología , Masculino , Trastornos de la Memoria/psicología , Persona de Mediana Edad , Pruebas Neuropsicológicas , Aprendizaje VerbalRESUMEN
Copper deficiency was induced in Sprague Dawley rats by dietary restriction to confirm and extend studies on copper, zinc-superoxide dismutase (Cu,Zn-SOD). Male rats restricted from copper in two models, a traditional postweanling model examining 50-day-old rats fed a low copper diet for 32 days (postnatal) and a gestational-lactational model examining 23-day-old male offspring of dams started on copper deficiency at day 7 of gestation (perinatal), showed signs of severe copper deficiency including anemia, and cardiac hypertrophy. Compared to control rats, copper-deficient rats exhibited lower copper concentrations in the liver, heart, brain, and kidney and lower Cu,Zn-SOD activity in the same organs with the exception of the brain in the postnatal model. In addition, there was a significant reduction in Cu,Zn-SOD protein detected by Western immunoblot proportional (r = 0.96) to the reduction in Cu,Zn-SOD activity. In the liver the reduction in Cu,Zn-SOD protein was approximately 50%. The reduction in Cu,Zn-SOD protein is likely due to a post-transcriptional mechanism as steady-state Cu,Zn-SOD mRNA levels measured by Northern hybridization were not altered by copper deficiency in any organ studied (liver, heart, and brain). Perhaps apo-Cu,Zn-SOD is degraded faster than fully metal-loaded enzyme. The loss of Cu,Zn-SOD activity and protein reduces the antioxidant defense capacity of copper-deficient organs.
Asunto(s)
Cobre/deficiencia , ARN Mensajero/genética , ARN Mensajero/metabolismo , Superóxido Dismutasa/genética , Superóxido Dismutasa/metabolismo , Animales , Secuencia de Bases , Cartilla de ADN/genética , Femenino , Masculino , Intercambio Materno-Fetal , Embarazo , Procesamiento Postranscripcional del ARN , Ratas , Ratas Sprague-Dawley , Distribución TisularRESUMEN
Perinatal copper (Cu) deficiency was studied by offering pregnant Sprague Dawley rats a basal diet low in copper, 0.44 mg/kg, and drinking water containing 0 (-Cu) or 20 (+Cu) mg Cu/L as CuSO4 starting at day 7 of gestation and continuing throughout lactation. To investigate dopamine-beta-monooxygenase (DBM) and tyrosine monooxygenase (TM) in adrenal gland and brain, offspring were weaned at Day 21 to treatments of their respective dams for 9 days. Offspring, 30 days old, of Cu-deficient (-Cu) dams were smaller, anemic, and had biochemical features characteristic of severe Cu deficiency. Adrenal DBM enzyme activity of 30-day-old -Cu rats was 40% higher than Cu-adequate (+Cu) rats and DBM protein levels, estimated by Western immunoblot, were 45% higher. Adrenal DBM mRNA levels of -Cu rats were 108% higher than +Cu rats. Adrenal TM protein levels of -Cu rats were 39% higher than +Cu rats. Hypothalamus DBM activity was significantly higher in -Cu than +Cu rats but no reproducible changes in DBM or TM protein levels could be detected by Western immunoblots. Diet history did not impact adrenal gland or hypothalamus levels of actin as detected on reblotted membranes. However, activity of the cuproenzyme Cu,Zn-superoxide dismutase was 50% lower and 30% lower, respectively, in extracts from rat adrenal gland and hypothalamus of -Cu than +Cu rats, indicating altered Cu status in the tissues studied. These data suggest that Cu deficiency is associated with increased formation of DBM and TM protein levels in adrenal gland. Further research will be required to determine the chemical signal responsible for this induction and if DBM or TM protein levels change in other tissues.
Asunto(s)
Cobre/deficiencia , Sistema Enzimático del Citocromo P-450/metabolismo , Dopamina beta-Hidroxilasa/metabolismo , Oxigenasas de Función Mixta/metabolismo , Preñez , Glándulas Suprarrenales/enzimología , Animales , Peso Corporal , Suplementos Dietéticos , Dopamina beta-Hidroxilasa/genética , Femenino , Hipotálamo/enzimología , Hipotálamo/patología , Masculino , Embarazo , Ratas , Ratas Sprague-DawleyRESUMEN
Dopamine beta-monooxygenase (DBM), a cuproenzyme, converts dopamine to norepinephrine in selected cells. Studies were conducted in albino rats to resolve the known paradox of DBM after copper deficiency in which metabolite analyses of tissues suggest lower activity, whereas direct assay of homogenates suggests enhanced activity. After 4 wk of postweanling copper deficiency, male Holtzman rats exhibited 1.4-fold higher adrenal DBM activity and 1. 8-fold higher adrenal DBM mRNA levels than copper-adequate rats. Mixing experiments did not support the existence of endogenous activators or inhibitors. Adrenal catecholamine content indicated lower norepinephrine, higher dopamine and unaffected epinephrine content in copper-deficient compared with copper-adequate rats. Studies in 22-d-old male Sprague-Dawley offspring of dams started on copper deficiency at d 7 of gestation indicated similar results for adrenal DBM mRNA, a 1.75-fold increase compared with copper-adequate pups. Adrenal dopamine content was higher in female copper-deficient offspring compared with controls, but norepinephrine was not lower. Medulla oblongata/pons DBM mRNA concentration was higher in 22-d-old copper-deficient female but not male rats compared with controls. Six weeks of copper repletion to the 22-d-old rats restored adrenal DBM mRNA levels to control values. Enzyme assay and RNA results are consistent with enhanced formation of DBM in adrenal gland and noradrenergic cell bodies of copper-deficient rats. The molecular signal may not be solely lower norepinephrine content because adrenal DBM mRNA changes were evident in both nutritional models, whereas the norepinephrine content was altered only in the postnatal model.