Buspirone impaired acquisition and retention in avoidance tasks: involvement of the hippocampus.

This study investigated the effects of buspirone on acquisition as well as formation and expression of memory in three different types of avoidance tasks. Rats were trained and tested on a one-trial inhibitory avoidance task, an 8-trial active avoidance task or the Morris water maze. Buspirone (5.0 mg/kg) was administered subcutaneously 30 min before training, immediately after training or 30 min before testing. Retention was tested at various times after training. In the inhibitory avoidance task, pretraining injections of buspirone produced a marked impairing effect on retention, posttraining injections of buspirone produced a moderate but time-dependent memory deficit. Pretest injections of buspirone suppressed retention performance. Such an effect was more pronounced in the 1-day test than in the 21-day test. Intra-hippocampal infusion of buspirone (5.0 micrograms) before testing suppressed expression of the 1-day, but not the 21-day, memory. In the active avoidance task and the Morris water maze, an injection of buspirone before training or testing also impaired acquisition or suppressed retention performance. These findings suggest that buspirone given at various times could compromise acquisition, consolidation and retrieval of affective memory and the hippocampus was involved in the retrieval effect.

Involvement of hippocampal NMDA and AMPA receptors in acquisition, formation and retrieval of spatial memory in the Morris water maze.

This study investigated the roles of hippocampal N-methyl-D-aspartate (NMDA) receptors and alpha-amino-3-hydroxyl-5-methyl-4-isoxazole propionate (AMPA) receptors in acquisition, consolidation and retrieval processes of spatial memory. Male Wistar rats with indwelling cannulae in the dorsal hippocampus received 4 training trials on the Morris water maze for consecutively 6 days. Rats received infusion of the NMDA receptor antagonist 2-amino-5-phosphonopentanoic acid (AP5) or the AMPA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) into the hippocampus under one of the three schedules: 5 min prior to each daily training session, immediately after each daily training session or 5 min prior to the final testing trial. Pretraining intra-hippocampal infusion of 5.0 micrograms AP5 retarded acquisition. The same dose of AP5 given after training had little effect but a higher dose (10.0 micrograms) did slow down progress in the acquisition curve. Pretest infusion AP5 failed to affect memory retrieval. Pretraining intra-hippocampal infusion of 1.0 micrograms CNQX also impaired acquisition, but posttraining infusion of CNQX at 1.0 or 2.0 micrograms had no effect. However, pretest infusion of 1.0 micrograms CNQX markedly impaired retrieval of the already-formed spatial memory. These findings taken together suggest that acquisition in a spatial task involves hippocampal NMDA and AMPA receptors, consolidation of spatial memory involves NMDA receptors and retrieving such memory involves AMPA receptors.

Involvement of amygdala N-methyl-D-asparate receptors in long-term retention of an inhibitory avoidance response in rats.

This study examined the involvement of amygdala N-methyl-D-aspartate (NMDA) receptors in long-term retention of an inhibitory avoidance response. Rats bearing chronic cannulae implanted into the basolateral amygdala were trained on a one-trial inhibitory avoidance task and tested for retention 21 days later. They received intra-amygdala injections of vehicle (Veh) or 0.25, 1.25 or 5.0 micrograms of a competitive NMDA antagonist-2-amino-5-phosphonopentoic acid (AP5) either 5 min before training, immediately after training or 5 min before testing. Results indicated that pretraining intra-amygdala injections of AP5 at all doses impaired retention performance profoundly. Intra-amygdala injections of AP5 immediately after training caused a dose-dependent retention deficit: 0.25 microgram induced no deficit and 5.0 micrograms induced a great deficit. Immediate posttraining intra-amygdala injections of a non-competitive NMDA antagonist MK-801, also impaired retention but MK-801 given 2 hrs after training had no significant effect. In contrast to the marked amnestic effect produced by pre- or posttraining intra-amygdala injections of AP5, intra-amygdala injections of AP5 given just before retention tests had no discernible effect on retention performance. The retention deficit induced by pretraining intra-amygdala injections of 1.25 micrograms AP5 was ameliorated completely by N-methyl-DL-aspartate (0.25 microgram), but also partially by norepinephrine (0.2 microgram) infused into the amygdala immediately after training. However, posttraining infusion 0.2 microgram norepinephrine failed to attenuate significantly the amnestic effect induced by 5.0 micrograms AP5. These findings, taken together, suggest that NMDA receptors in the amygdala are normally involved in memory formation processing of affective experience.