RESUMO
Male Wistar rats received bilateral infusions of vehicle (VEH) or aminophosphonopentanoic acid (AP5), an N-metil-D-aspartate (NMDA) receptor antagonist, into the dorsal hippocampus immediately after inhibitory avoidance (IA) training. Intrahippocampal infusion of AP5 blocked 24 h IA retention. In the second experiment, animals were preexposed to the IA training context 24 h prior to training and received an infusion of either VEH or AP5 immediately after the preexposure trial and a second infusion of VEH or AP5 immediately after IA training. AP5 did not affect retention in animals preexposed to the IA box and given VEH after preexposure, but blocked retention when given after both preexposure and training. AP5 impaired retention in rats preexposed to an environment distinct from the IA box. These results suggest that NMDA receptors in the dorsal hippocampus mediate the formation of a contextual representation of the task environment.
Assuntos
Aprendizagem da Esquiva/fisiologia , Hipocampo/fisiologia , Memória/fisiologia , Receptores de N-Metil-D-Aspartato/metabolismo , 2-Amino-5-fosfonovalerato/metabolismo , Animais , Antagonistas de Aminoácidos Excitatórios/metabolismo , Hipocampo/anatomia & histologia , Masculino , Ratos , Ratos WistarRESUMO
METHOD: Starting from the studies of Conrad on early schizophrenia, we quantified the gestaltic alteration that he has described using a visual-motor gestaltic test (Bender test) in acute and chronic schizophrenic patients. We observed that rotations and distortions were significantly higher in chronic patients, and perseverations in acute patients. Global scores and time employed showed significant differences in both groups when compared with controls. Time is classically considered a compensation in the failure. We observed that the Bender gestaltic test allows quantification of perceptual alterations due to the loss of the objective structure of the perception in schizophrenic patients. Aiming to reproduce these findings in an animal model, we proposed a study of pharmacological modification of nucleus accumbens septi (Acc) neurotransmission, traditionally linked with physiopathology of schizophrenia. In this way, we developed a discrimination shape model in a skinner box in trained pigeons, bilaterally implanted in Acc by stereotaxic surgery. CONCLUSIONS: The antagonists of N-methyl-D-aspartic acid (NMDA) glutamatergic receptor induced a significant decrease in performance in the discrimination task, and a significant increase in correcting trials. The last parameter was considered a perseveration, manifestation of a behavioral inflexibility in relationship with environmental changes. The glutamatergic blockade of Acc in rats using a passive avoidance task induced a disturbance in acquisition, and the same procedure in the plus maze test led to a significant decrease in anxiety levels, suggesting additional homologies with schizophrenic psychoses.
Assuntos
2-Amino-5-fosfonovalerato/análogos & derivados , Percepção/fisiologia , Esquizofrenia/fisiopatologia , Transtornos de Sensação/fisiopatologia , 2-Amino-5-fosfonovalerato/metabolismo , Animais , Córtex Cerebral/anatomia & histologia , Córtex Cerebral/metabolismo , Antagonistas de Aminoácidos Excitatórios/metabolismo , Humanos , Testes Neuropsicológicos , Núcleo Accumbens/anatomia & histologia , Núcleo Accumbens/metabolismoRESUMO
Extensive evidence suggests that N-methyl-D-aspartate (NMDA) glutamate receptor channels in the amygdala are involved in fear-motivated learning, and infusion of NMDA receptor antagonists into the amygdala blocks memory of fear-motivated tasks. Recent studies have shown that previous training can prevent the amnestic effects of NMDA receptor antagonists on spatial learning. In the present study, we evaluated whether infusion of the NMDA antagonist D,L-2-amino-5-phosphonopentanoic acid (AP5) into the basolateral nucleus of the amygdala (BLA) impairs reinforcement of inhibitory avoidance learning in rats given previous training. Adult male Wistar rats (220-310 g) were bilaterally implanted under thionembutal anesthesia (30 mg/kg, i.p.) with 9.0-mm guide cannulae aimed 1.0 mm above the BLA. Infusion of AP5 (5.0 microg) 10 min prior to training in a step-down inhibitory avoidance task (0.4 mA footshock) blocked retention measured 24 h after training. When infused 10 min prior to a second training session in animals given previous training (0.2 mA footshock), AP5 blocked the enhancement of retention induced by the second training. Control experiments showed that the effects were not due to alterations in motor activity or footshock sensitivity. The results suggest that NMDA receptors in the basolateral amygdala are involved in both formation of memory for inhibitory avoidance and enhancement of retention in rats given previous training.