Vasopressin V1b receptor knockout reduces aggressive behavior in male mice

Scott Wersinger¹, Edward I. Ginns², Anne-Marie O'Carroll³, Stephen J. Lolait³ ,W. Scott Young ¹

¹ Section on Neural Gene Expression, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892; ²Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, MA, USA; ³University Research Centre For Neuroendocrinology, University of Bristol, UK

Mol. Psychiat. 7: 975-84, 2002.

Increased aggression is commonly associated with many neurological and psychiatric disorders. Current treatments are largely empirical and are often accompanied by severe side effects, underscoring the need for a better understanding of the neural bases of aggression. Vasopressin, acting through its 1a receptor subtype, is known to affect aggressive behaviors. The vasopressin 1b receptor (V1bR) is also expressed in the brain, but has received much less attention due to a lack of specific drugs. Here we report that mice without the V1bR exhibit markedly reduced aggression and modestly impaired social recognition. By contrast, they perform normally in all the other behaviors that we have examined, such as sexual behavior, suggesting that reduced aggression and social memory are not simply the result of a global deficit in sensorimotor function or motivation. Fos-mapping within chemosensory responsive regions suggests that the behavioral deficits in V1bR knockout mice are not due to defects in detection and transmission of chemosensory signals to the brain. We suggest that V1bR antagonists could prove useful for treating aggressive behavior seen, for example, in dementias and traumatic brain injuries.
The entire manuscript as a 180kb PDF file is also available. Further studies we have done are listed here.

Wildtype mice exhibit aggressive behavior, whereas eliminating the vasopressin V1b receptor reduces aggressive behavior

Click on image to see video (3.8MB). Apple's QuickTime is needed to view this movie.

Two wildtype non-littermates were placed in the cage on the left and two V1bR knockout non-littermates in the cage on the right. The wildtype mice soon began to show aggressive signs, such as tail rattling, and were separated when they began to fight. The knockout mice in the other cage were watched for 45 minutes (a little over 3 minutes are shown here) and no aggressive behavior was observed.

Return to the SNGE Home Page