Submitted on October 2, 2007
Accepted on February 20, 2008
Alcohol preference in mice lacking the Avpr1a vasopressin receptor
Atsushi Sanbe1*, Norio Takagi2, Yoko Fujiwara1, Junji Yamauchi1, Toshiya Endo1, Reiko Mizutani1, Satoshi Takeo2, Gozoh Tsujimoto3, and Akito Tanoue1
1 Pharmacology, National Research Institute for Child Health and Development, Setagaya, Tokyo, Japan
2 Pharmacology, Tokyo University of Pharmacy and Life Science, Hachioji, Tokyo, Japan
3 Genomic Drug Discovery Science, Kyoto University, Kyoto, Kyoto, Japan
* To whom correspondence should be addressed. E-mail: asanbe{at}nch.go.jp.
[Arg8]-Vasopressin (Avp), a nonapeptide hormone, is known to regulate blood pressure, water balance, and a variety of behaviors such as anxiety, aggression, and bonding. Although some evidence that Avp modifies ethanol consumption and some of the effects of ethanol on behavior have been reported, the role of Avp in alcohol consumption and preference is poorly understood. The Avp 1a receptor (Avpr1a) is ubiquitously expressed in the central nervous system. To determine the role of Avp signaling on the behavioral effects of alcohol, we examined voluntary ethanol consumption in mice with targeted disruptions of the Avpr1a (Avpr1a KO) gene. Avpr1a KO mice displayed both increased ethanol consumption and preference compared with the wild-type (WT) mice. The enhanced ethanol consumption was dramatically and reversibly reduced by treatment with NMDA antagonists. Basal glutamate release was elevated around the striatum in Avpr1a KO mice. The elevation of extracellular glutamate was also produced in WT mice by local application of an Avpr1a antagonist though a dialysis probe, and this elevation was quickly reversed by stopping the perfusion. These results suggest that Avp can inhibit the release of glutamate from the presynaptic terminal via the Avp 1a receptor and that elevation of glutamate levels owing to loss of the inhibitory effect via Avp-Avpr1a signaling may play an important role in the preference for ethanol.
