title: Disruption of the prepulse inhibition of the startle reflex in vasopressin V1b receptor knockout mice: reversal by antipsychotic drugs.
abstract: In the present study, we investigated whether mice lacking the arginine vasopressin (AVP) V1b receptor (V1bR) exhibit deficits of prepulse inhibition (PPI) of the startle reflex, reminiscent of the sensorimotor gating deficits observed in a large majority of schizophrenic patients. V1bR knockout (KO) mice displayed significantly reduced levels of PPI of the startle reflex. In addition to PPI deficits, V1bR KO mice showed increased acoustic startle response. However, acoustic startle response was not significantly correlated to the PPI of the startle reflex in V1bR KO mice. V1bR KO mice also showed a decrease in basal levels of extracellular dopamine (DA) in the medial prefrontal cortex, which is thought to be an important brain region for PPI. Moreover, PPI deficits observed in the V1bR KO mice are significantly reversed by atypical antipsychotics such as risperidone and clozapine but not by a typical neuroleptic haloperidol, like in schizophrenic patients. By contrast, we did not observe any significant differences between V1bR KO mice and wild-type mice in the open-field, light/dark, elevated plus maze, and forced swimming tests. The results of the present study indicate that V1bR may be involved in the regulation of PPI of the startle reflex. The V1bR has been considered an important molecular target for the development of antipsychotic drugs.
authors.affiliation: Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Nobuaki
authors.initials: N
authors.lastname: Egashira
authors.forename: Akito
authors.initials: A
authors.lastname: Tanoue
authors.forename: Fuminori
authors.initials: F
authors.lastname: Higashihara
authors.forename: Hiroko
authors.initials: H
authors.lastname: Fuchigami
authors.forename: Kazunori
authors.initials: K
authors.lastname: Sano
authors.forename: Kenichi
authors.initials: K
authors.lastname: Mishima
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Fukue
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Nagai
authors.forename: Yukio
authors.initials: Y
authors.lastname: Takano
authors.forename: Gozoh
authors.initials: G
authors.lastname: Tsujimoto
authors.forename: Jeanne
authors.initials: J
authors.lastname: Stemmelin
authors.forename: Guy
authors.initials: G
authors.lastname: Griebel
authors.forename: Katsunori
authors.initials: K
authors.lastname: Iwasaki
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Ikeda
authors.forename: Ryoji
authors.initials: R
authors.lastname: Nishimura
authors.forename: Michihiro
authors.initials: M
authors.lastname: Fujiwara
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004347:Drug Interactions; D005106:Exploratory Behavior / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D017551:Microdialysis / Q000379:methods; D009433:Neural Inhibition / Q000187:drug effects*; D017483:Receptors, Vasopressin / Q000172:deficiency*; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D013223:Statistics as Topic; D013550:Swimming
chemical_list: D014150:Antipsychotic Agents; D017483:Receptors, Vasopressin