Lidocaine reversible inactivation of the median raphe nucleus has no effect on reference memory but enhances working memory versions of the Morris water maze task

Numerous studies in the past have dealt with the role of serotonergic syste m lesions in tasks aimed at measurement of cognitive behavior, but the lite rature concerning the role of serotonin in cognition remains controversial. Rats with electrolytic lesions of the median raphe nucleus (MRN) were foun d to display a profound impairment in both the acquisition and retention of spatial memory task. In this study, the lidocaine inactivation was employe d to evaluate the involvement of the rat's median raphe nucleus in referenc e and working memory versions of the Morris water maze (MWM) task. Lidocain e (0.5 mu l, 2%) was injected through a single cannula aimed at the MRN; co ntrol groups were treated in the same way with a 0.5 mu l injection of sali ne. In Experiment 1, rats were trained in a reference memory version of the MWM with two blocks of four trials per day for three consecutive days, wit h intra-cerebral injection made 5 mill before training. No significant diff erence was found. In Experiment 2, intra-cerebral injection was applied imm ediately after two blocks of four trials, and in Experiment 3, the drug was injected 5 min before retention test in rats that had received eight trial s per day on three consecutive days. Again, no significant difference betwe en control and treatment groups was found. These results indicate that MRN has no role in acquisition, consolidation and retrieval of spatial referenc e memory. In subsequent experiments, rats were trained in a working memory version of the MWM task to find a new target position in trial 1, and retri eval was tested 75 min later. MRN inactivation 5 min before (Experiment 4) and immediately after the acquisition trial (Experiment 5) enhanced spatial working memory. It is concluded that normal activity of the MRN has no rol e in formation and retrieval of reference memory, but it has an inhibitory role in working memory. Our results are confirmed with other studies sugges ting that the serotonergic system has a different role in long-term and sho rt-term memory. Interaction with other neurotransmitter systems like acetyl choline may be involved in this case. (C) 2000 Elsevier Science B.V. All ri ghts reserved.