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 system lesions in tasks aimed at measurement of cognitive behavior, but the literature concerning the role of serotonin in cognition remains controversial. Rats with electrolytic lesions of the median raphe nucleus (MRN) were found to display a profound impairment in both the acquisition and retention of spatial memory task. In this study, the lidocaine inactivation was employed to evaluate the involvement of the rat's median raphe nucleus in reference and working memory versions of the Morris water maze (MWM) task. Lidocaine (0.5 microl, 2%) was injected through a single cannula aimed at the MRN; control groups were treated in the same way with a 0.5 microl injection of saline. 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, with intra-cerebral injection made 5 min before training. No significant difference was found. In Experiment 2, intra-cerebral injection was applied immediately 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 trials per day on three consecutive days. Again, no significant difference between control and treatment groups was found. These results indicate that MRN has no role in acquisition, consolidation and retrieval of spatial reference 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 retrieval 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 role in formation and retrieval of reference memory, but it has an inhibitory role in working memory. Our results are confirmed with other studies suggesting that the serotonergic system has a different role in long-term and short-term memory. Interaction with other neurotransmitter systems like acetylcholine may be involved in this case.

Reversible inactivation of the median raphe nucleus enhances consolidation and retrieval but not acquisition of passive avoidance learning in rats.

Involvement of median raphe nucleus (MRN) in acquisition, consolidation and retrieval of passive avoidance (PA) was investigated with functional suppression of this area by lidocaine. Rats carrying a chronically implanted cannula aimed at the MRN were trained on a step-through passive avoidance task and received intra-MRN injection of lidocaine or saline 5 min before training or 5, 90 and 360 min after acquisition trial or 5 min before the retrieval test. Lidocaine MRN inactivation had no effect on PA learning. Lidocaine injected 5 and 90 min after the acquisition trial significantly enhanced avoidance of the dark compartment in comparison with the control group injected with saline. But PA retention was not affected by lidocaine injected 360 min after acquisition or 5 min before training. Retention latency significantly increased, when lidocaine injected 5 min before retrieval test. Step-through latency of naive rats was not affected by MRN blockade. Furthermore, reversible inactivation of MRN did not have a significant effect on locomotor activity. Our results indicate that the MRN contributes to PA consolidation at least until 90 min after acquisition and involves in PA retrieval. It is concluded that functional ablation of the MRN may disrupt the inhibitory actions of MRN projections to sub-cortical circuits participating in PA memorization and retrieval.