MEMORY IMPAIRMENT IN RATS WITH GLUTAMATERGIC TEMPORAL SYSTEMS DISRUPTED IS ATTENUATED BY D-CYCLOSERINE - EFFECTS OF POSTOPERATIVE TIME OF INJECTION

Disconnection of the neural fibers between the temporal cortex (TC) an d the lateral entorhinal cortex (LEC) in rats causes impaired memory a nd reduced concentration of glutamate in both the TC and the LEC. Admi nistration of the glutamatergic agonists NMDA, glycine, or AMPA improv es retroactive memory, which is more severely impaired by TC/LEC lesio ns than proactive memory in a three-choice brightness discrimination t ask. It has not been determined, however, whether there are positive e ffects of agonists given at a particular time of injection. The purpos e of the present study was to address this issue by applying (on Posto perative Days 0-12) the partial agonist D-cycloserine, which may be of special clinical interest. The results show that injections given sho rtly after surgery (Days 0-1) or just prior to retrieval (Day 12) are much more effective than injections given between these extremes. Inje ctions given on Postoperative Day 8 had no effect at all, whereas a st epwise increase in effects was seen toward both Day 0 and Day 12. It i s suggested that the action profile of cycloserine may reflect effects of both functional and pharmacological mechanisms. Cycloserine may re present a relevant means of treatment of dementia.