RESUMEN
Adult rats treated IP with domoic acid at 0, 0.22, 0.65, or 1.32 mg/kg were tested for passive avoidance (PA), auditory startle (AS), or conditioned avoidance (CAR) behaviors. Clinical signs were observed only at the 1.32 mg/kg dose level. Within 24 h of dosing, rats surviving a dose of 1.32 mg/kg exhibited transient decreased body weight and exaggerated AS responding. Startle latency and habituation, PA, and CAR were not affected. Examination of brains from six rats per group revealed a subset (2/6) of animals receiving 1.32 mg/kg domoic acid with degenerating neurons in the hippocampal CA1/CA3 subregions and gliosis. The decreased body weight and increased startle suggest a hyperreactivity syndrome possibly related to neuronal degeneration in the hippocampus. In a separate experiment, domoic acid at an IP dose of 0.93 mg/kg was found to produce hypomotility in addition to a decrease in body weight. Both effects were reduced by pretreatment with scopolamine (2 mg/kg), but not with caffeine (30 mg/kg), indicating a possible cholinergic involvement in domoate's toxicity.
Asunto(s)
Reacción de Prevención/efectos de los fármacos , Hipocampo/patología , Ácido Kaínico/análogos & derivados , Neurotoxinas/toxicidad , Reflejo de Sobresalto/efectos de los fármacos , Estimulación Acústica , Análisis de Varianza , Animales , Astrocitos/efectos de los fármacos , Astrocitos/patología , Peso Corporal , Condicionamiento Operante , Relación Dosis-Respuesta a Droga , Habituación Psicofisiológica , Hipocampo/efectos de los fármacos , Inyecciones Intraperitoneales , Ácido Kaínico/toxicidad , Masculino , Ratas , Ratas Sprague-DawleyRESUMEN
Excessive dietary Fe is known to be toxic, but the extent of neurobiological involvement is not clear. In the present study male weanling rats were fed diets containing Fe at 35 (control), 350, 3500, or 20000 ppm for 12 wk. An Fe-deficient group (4 ppm) was included for comparison. Rats were tested for behavioral and body weight changes at various times after initiation of diets, and liver and brain nonheme Fe were measured at term. Excess dietary Fe, primarily at 20000 ppm, significantly decreased activity, habituation, reflex startle, and conditioned avoidance response performance, and enhanced prepulse modulation of startle. Body weights were also markedly decreased. Fe-deficient animals showed similar behavioral effects but more moderate body weight changes. Liver nonheme Fe varied directly with dietary levels. Whole-brain nonheme Fe was significantly reduced in Fe-deficient animals but increased only at the 20000-ppm level. Homeostatic mechanisms appear to regulate whole-brain Fe more effectively under conditions of dietary Fe overload than under conditions of Fe deficiency. The behavioral changes associated with dietary Fe overload may represent secondary consequences of systemic toxicity.
Asunto(s)
Conducta Animal/efectos de los fármacos , Encéfalo/efectos de los fármacos , Sobrecarga de Hierro/fisiopatología , Hierro/toxicidad , Anemia Ferropénica/patología , Anemia Ferropénica/fisiopatología , Animales , Reacción de Prevención/efectos de los fármacos , Reacción de Prevención/fisiología , Conducta Animal/fisiología , Encéfalo/patología , Condicionamiento Clásico/efectos de los fármacos , Condicionamiento Clásico/fisiología , Relación Dosis-Respuesta a Droga , Hierro/metabolismo , Sobrecarga de Hierro/patología , Masculino , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Ratas , Ratas Sprague-Dawley , Reflejo de Sobresalto/efectos de los fármacos , Reflejo de Sobresalto/fisiologíaRESUMEN
The multipup homing procedure (MHP) is a rapid test for olfactory discrimination performance that can be run on an entire 8-pup litter of neonatal rats in 8 min. Performance improved developmentally with age, and females tended to perform better than males. The MHP was examined for its usefulness in detecting early postnatal effects of low-level prenatal exposure to chlorpromazine (CPZ) or d-amphetamine (AMPH). CPZ increased response latencies in both males and females, but AMPH had no significant effects. The MHP appears promising for use in behavioral teratological assessment of neurobehavioral function.