Effects of inactivation of serotonergic neurons of the median raphe nucleus on learning and performance of contextual fear conditioning

Several studies have shown that the median raphe nucleus (MRN) is involved in anxiety. However, no study assessed the role of 5-HT mechanisms of MRN in both freezing and fear-potentiated startle (FPS) within a single form of conditioned learning. In this work we examined the effects of neurotoxic lesions of the MRN with NMDA on freezing and FPS of rats submitted to a contextual fear conditioning paradigm, in which they were tested in the same chamber where they received foot-shocks 24 h before. Compared to controls NMDA-injected rats showed a reduction of freezing and FPS in response to contextual cues. Next, we examined the effects of stimulation of 5-HT1A somatodendritic autoreceptors of the MRN with local injections of 8-OH-DPAT either before training or testing sessions conducted 2 or 24 h post-conditioning. Pre-training injections of 8-OH-DPAT intra-MRN reduced both freezing and FPS whereas post-training injections reduced only freezing to the aversive context without changing the FPS. Thus, freezing is easily disrupted by post-training MRN injections of 8-OH-DPAT while memory for FPS remained unchanged. It is proposed that the consolidation of contextual conditioned fear promoting freezing takes place through a slow mechanism of transference of information through 5-HT mechanisms of the MRN-hippocampus pathway. On the other hand, a rapid fear conditioning process operates for FPS, probably through other pathways.