RESUMEN
Prenatal morphine exposure throughout pregnancy can induce a series of neurobehavioral and neurochemical disturbances by affecting central nervous system development. This study was designed to investigate the effects of an enriched environment on behavioral deficits and changes in hippocampal brain-derived neurotrophic factor (BDNF) levels induced by prenatal morphine in rats. On pregnancy days 11-18, female Wistar rats were randomly injected twice daily with saline or morphine. Offspring were weaned on postnatal day (PND) 21. They were subjected to a standard rearing environment or an enriched environment on PNDs 22-50. On PNDs 51-57, the behavioral responses including anxiety and depression-like behaviors, and passive avoidance memory as well as hippocampal BDNF levels were investigated. The light/dark (L/D) box and elevated plus maze (EPM) were used for the study of anxiety, forced swimming test (FST) was used to assess depression-like behavior and passive avoidance task was used to evaluate learning and memory. Prenatal morphine exposure caused a reduction in time spent in the EPM open arms and a reduction in time spent in the lit side of the L/D box. It also decreased step-through latency and increased time spent in the dark side of passive avoidance task. Prenatal morphine exposure also reduced immobility time and increased swimming time in FST. Postnatal rearing in an enriched environment counteracted with behavioral deficits in the EPM and passive avoidance task, but not in the L/D box. This suggests that exposure to an enriched environment during adolescence period alters anxiety profile in a task-specific manner. Prenatal morphine exposure reduced hippocampal BDNF levels, but enriched environment significantly increased BDNF levels in both saline- and morphine-exposed groups. Our results demonstrate that exposure to an enriched environment alleviates behavioral deficits induced by prenatal morphine exposure and up-regulates the decreased levels of BDNF. BDNF may contribute to the beneficial effects of an enriched environment on prenatal morphine-exposed to rats.
Asunto(s)
Analgésicos Opioides/toxicidad , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Ambiente , Hipocampo/metabolismo , Trastornos Mentales , Morfina/toxicidad , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Factores de Edad , Análisis de Varianza , Animales , Reacción de Prevención/efectos de los fármacos , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Masculino , Aprendizaje por Laberinto , Trastornos Mentales/metabolismo , Trastornos Mentales/enfermería , Trastornos Mentales/patología , Embarazo , Ratas , Ratas Wistar , Natación/psicología , Factores de TiempoRESUMEN
The beneficial effects of exercise on learning and memory are well documented but the effects of prenatal exposure to maternal exercise on offspring are not clear yet. Using a two-trial-per-day Morris water maze for five consecutive days, succeeded by a probe trial 2 days later we showed that maternal voluntary exercise (wheel running) by pregnant rats increased the acquisition phase of the pups' learning. Maternal forced swimming by pregnant rats increased both acquisition and retention phases of the pups' learning. Also we found that the rat pups whose mother was submitted to forced-swimming during pregnancy had significantly higher brain, liver, heart and kidney weights compared with their sedentary counterparts. On the other hand we estimated the cell number of different regions of the hippocampus in the rat pups. We found that both exercise models during pregnancy increased the cell number in cornus ammonis subregion 1 (CA1) and dentate gyrus of the hippocampus in rat pups. To determine the role that noradrenergic and serotonergic neurotransmission and N-methyl-D-aspartate (NMDA) receptors hold in mediation of the maternal exercise in offspring, we used N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), p-chloroamphetamine (PCA) and MK-801 to eliminate or block the above systems, respectively. Blocking the NMDA receptors, significantly abolished learning and memory in rat pups from all three experimental groups. Elimination of noradrenergic or serotonergic input did not significantly attenuate the learning and memory in rat pups whose mothers were sedentary, while it significantly reversed the positive effects of maternal exercise during pregnancy on rat pups' learning and memory. The presented results suggest that noradrenergic and serotonergic systems in offspring brain seem to have a crucial specific role in mediating the effects of maternal physical activity during pregnancy on rat pups' cognitive function in both models of voluntary and forced exercise.
Asunto(s)
Conducta Materna/fisiología , Memoria/fisiología , Norepinefrina/metabolismo , Condicionamiento Físico Animal/fisiología , Serotonina/metabolismo , Percepción Espacial/fisiología , Análisis de Varianza , Animales , Animales Recién Nacidos , Conducta Animal , Bencilaminas/toxicidad , Corticosterona/sangre , Femenino , Masculino , Aprendizaje por Laberinto/efectos de los fármacos , Memoria/efectos de los fármacos , Embarazo , Ratas , Ratas Wistar , Tiempo de Reacción/fisiología , Percepción Espacial/efectos de los fármacos , Natación , p-Cloroanfetamina/toxicidadRESUMEN
Previous studies indicated that stress levels of glucocorticoid hormones (cortisol in humans, and corticosterone in rodents) induce impairment of long-term memory retrieval, but the underlying mechanisms (genomic or nongenomic) are not clear. To clarify this issue, we investigated the involvement of brain corticosteroid receptors and protein synthesis in the corticosterone-induced impairment of memory retrieval. Young rats were trained in the water maze task with six trials per day for 6 consecutive days. Retention of the spatial training was assessed 24 h after the last training session with a 60-s probe trial. Experiments included intraventricular injections of anisomycin, a specific protein synthesis inhibitor or specific antagonists for both types of corticocosteroid receptors (mineralocorticoid receptor, MR, and glucocorticoids receptor, GR) before corticosterone administration shortly before retention testing. The results showed that administration of anisomycin did not change the corticosterone response. Administration of the MR, but not GR, antagonist blocked the corticosterone-induced response dose dependently. These findings provide evidence for the view that glucocorticoids impair memory retrieval through nongenomic mechanisms involving an interaction with central MRs.