title: Metaplastic regulation of the median raphe nucleus via serotonin 5-HT1A receptor on hippocampal synaptic plasticity is associated with gender-specific emotional expression in rats.
abstract: 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-HT1A 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.
authors.affiliation: Department of Pharmacology, Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
authors.forename: Sumitaka
authors.initials: S
authors.lastname: Inoue
authors.forename: Hiroki
authors.initials: H
authors.lastname: Shikanai
authors.forename: Machiko
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hiraide
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Saito
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Yanagawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Kei-ichi
authors.initials: K
authors.lastname: Shimamura
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
mesh_terms: D000818:Animals; D003213:Conditioning, Psychological / Q000502:physiology; D019260:Expressed Emotion / Q000502:physiology*; D005239:Fear / Q000502:physiology; D005260:Female; D006624:Hippocampus / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects; D008297:Male; D001523:Mental Disorders / Q000209:etiology / Q000523:psychology; D008679:Metaplasia / Q000235:genetics; D009473:Neuronal Plasticity / Q000235:genetics* / Q000502:physiology*; D011903:Raphe Nuclei / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D044263:Receptors, Serotonin, 5-HT1 / Q000502:physiology*; D012701:Serotonin / Q000378:metabolism; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000150:complications; D013569:Synapses / Q000502:physiology*
chemical_list: D044263:Receptors, Serotonin, 5-HT1; D012701:Serotonin