1. ¹Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
2. ²Department of Molecular, Cell Pharmacology, National Research Institute for Child Health and Development, Tokyo, Japan
3. ³Department of Psychiatry, Fukuoka University School of Medicine, Fukuoka University, Fukuoka, Japan
4. ⁴Department of Pharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan
5. ⁵Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto, Japan
6. ⁶Sanofi-Aventis, Bagneux, France

Correspondence: Dr M Fujiwara, Department of Neuropharmacology, Faculty of Pharmaceutical Sciences, Fukuoka University, 8-19-1, Nanakuma, Fukuoka 814-0180, Japan. Tel: 81 92 871 6631 (ext. 6600); Fax: 81 92 863 0389; E-mail: mfuji@fukuoka-u.ac.jp

Received 8 November 2004; Revised 12 April 2005; Accepted 22 April 2005; Published online 1 June 2005.

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.