HIPPOCAMPAL 5-HT RECEPTORS AND CONSOLIDATION OF STRESSFUL MEMORIES

It has been suggested that postsynaptic 5-HT1A receptors in the hippoc ampus, innervated by 5-HT neurons localized in the median raphe nucleu s, mediate adaptive or coping responses to aversive events and that dy sfunction of this system is related to symptoms of depression. To test this hypothesis we investigated the expression of c-fos mRNA in anima ls submitted to immobilization stress. The results showed that c-fos m RNA expression is significantly increased in the dentate gyrus and CA1 -CA3 regions of the hippocampus after 30 min of forced restraint, sugg esting that this structure is activated during stress. To investigate the role of 5-HT neurotransmission in the hippocampus on adaptation to aversive events we immobilized rats for 2 h and tested them 24 h late r in an elevated plus-maze. Our results showed that the previous restr aint period decreases exploration of open arms in the maze. This effec t was reversed by bilateral microinjection of zimelidine (20 and 100 n mol), a 5-HT re-uptake blocker, or 8-OH-DPAT (3 nmol), a 5-HT1A agonis t, into the dorsal hippocampus immediately after restraint. These resu lts are compatible with the idea that postsynaptic 5-HT1A receptors lo cated in the hippocampus participate in the development of tolerance t o aversive events.