Female gastrin-releasing peptide receptor (GRP-R)-deficient mice exhibit altered social preference for male conspecifics: implications for GRP/GRP-R modulation of GABAergic function.

We studied female GRP-R-deficient mice with respect to olfactory function and social behavior toward male conspecifics. Results of a food exploration test (hidden cookie method) revealed that the olfactory ability of these mutant mice is identical to that of wild-type mice. However, when preference toward either a socially dominant or subordinate male mouse was assessed in a social preference test, wild-type mice showed a greater preference for socially dominant males than did GRP-R-deficient mice. In contrast, in a social investigation test to an anesthetized male mouse, GRP-R-deficient mice exhibited greater investigatory behavior toward the target male than did wild-type mice. When female C57BL/6J mice were given diazepam (0, 1, 2 or 4 mg/kg, i.p.), their investigatory behavior to the anesthetized male target was increased in a dose-dependent manner. Conversely, i.p. administration of bicuculline (1 mg/kg) significantly decreased the social investigatory behavior of female GRP-R-deficient mice, but not of wild-type mice. These results indicate that female GRP-R-deficient mice exhibit altered responsiveness to male conspecifics relative to their wild-type counterparts, and suggest that this outcome may be attributable, at least in part, to altered GABAergic function in these mutant mice.