Metaplastic regulation of the median raphe nucleus via serotonin 5-HT 1A receptor on hippocampal synaptic plasticity is associated with gender-specific emotional expression in rats

Gender differences in psychiatric disorders are considered to be associated with the serotonergic (5-htergic) system; however the underlying mechanisms have not been clearly elucidated. in this study,possible involvement of the median raphe nucleus (mrn)-hippocampus 5-htergic system in gender-specific emotional regulation was investigated,focusing on synaptic plasticity in rats. a behavioral study using a contextual fear conditioning (cfc) paradigm showed that the females exhibited low anxiety-like behavior. extracellular 5-ht levels in the hippocampus were increased by cfc only in the males. long-term potentiation (ltp) in the hippocampal ca1 field was suppressed after cfc in the males,which was mimicked by the synaptic response to mrn electrical stimulation. in the mrn,5-ht immunoreactive cells significantly increased in the females compared with those in the males. pretreatment with the 5-ht 1a receptor agonists tandospirone (10 mg/kg,i.p.) and 8-oh dpat (3 mg/kg,i.p.) significantly suppressed ltp induction in the males. synaptic responses to cfc and 5-ht1a receptor interventions were not observed in the females. these results suggest that the metaplastic 5-htergic mechanism via 5-ht1a receptors in the mrn-hippocampus pathway is a key component for gender-specific emotional regulation and may be a cause of psychiatric disorders associated with vulnerability or resistance to emotional stress. © the japanese pharmacological society.