title: The serotonergic projection from the median raphe nucleus to the ventral hippocampus is involved in the retrieval of fear memory through the corticotropin-releasing factor type 2 receptor.
abstract: Several different studies have separately established that serotonin, corticotropin-releasing factor (CRF) receptors, and the hippocampus are involved in fear memory retrieval. The main aim of this study is to connect these separate studies. To assess the levels of anxiety/fear, we used the contextual fear-conditioning test and the elevated plus maze test as memory-dependent and memory-independent tasks, respectively. We injected CRF receptor antagonists or vehicle into the median raphe nucleus (MRN) 10 min before behavioral tests. As a result, 1000 ng of astressin 2B (CRF(2) receptor antagonist), but not 250 ng of antalarmin (CRF(1) receptor antagonist), significantly suppressed the expression rate of freezing behavior in the contextual fear-conditioning test. However, in the elevated plus maze test, there was no difference between astressin 2B-injected rats and saline-injected rats in the time spent in open arms. Neither the amount of exploratory behavior nor the moving distance in the EPM of astressin 2B-injected rats differed from that of vehicle-injected rats. Moreover, when we assessed the extracellular serotonin release in the ventral hippocampus in freely moving rats through in vivo microdialysis, it was shown that the blockade of the CRF(2) receptor in the MRN suppressed serotonin release in the ventral hippocampus during fear memory retrieval. These results indicated that endogenous CRF and/or related ligands that were released in the MRN could activate the CRF(2) receptor and stimulate serotonin release in the ventral hippocampus, thereby inducing fear memory retrieval.
authors.affiliation: Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ohmura
authors.forename: Takeshi
authors.initials: T
authors.lastname: Izumi
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Iku
authors.initials: I
authors.lastname: Tsutsui-Kimura
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshida
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
mesh_terms: D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism / Q000494:pharmacology; D005239:Fear / Q000502:physiology*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008568:Memory / Q000502:physiology*; D009434:Neural Pathways / Q000166:cytology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D009483:Neuropsychological Tests; D010446:Peptide Fragments / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018019:Receptors, Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012701:Serotonin / Q000378:metabolism*
chemical_list: C101531:CRF receptor type 2; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D018019:Receptors, Corticotropin-Releasing Hormone; C104416:astressin; D012701:Serotonin; D003346:Corticotropin-Releasing Hormone