Disruption of the prepulse inhibition of the startle reflex in vasopressin V1b receptor knockout mice: reversal by antipsychotic drugs.
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.
Egashira
Nobuaki
N
Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
Tanoue
Akito
A
Higashihara
Fuminori
F
Fuchigami
Hiroko
H
Sano
Kazunori
K
Mishima
Kenichi
K
Fukue
Yoshihiko
Y
Nagai
Hiroshi
H
Takano
Yukio
Y
Tsujimoto
Gozoh
G
Stemmelin
Jeanne
J
Griebel
Guy
G
Iwasaki
Katsunori
K
Ikeda
Tomoaki
T
Nishimura
Ryoji
R
Fujiwara
Michihiro
M
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
D014150:Antipsychotic Agents; D017483:Receptors, Vasopressin