Diminished Anxiety- and Depression-Related Behaviors in Mice with Selective Deletion of the<i>Tac1</i>Gene

Abstract

The tachykinin neuropeptide substance P and its receptor neurokinin 1 have been implicated in the regulation of many physiological and pathological processes, including the control of emotional behaviors. The present study examines mice with a targeted deletion of the Tac1 gene, which encodes the neuropeptides substance P and neurokinin A, in animal models relevant to depressive illness and anxiety. In depression-related paradigms, Tac1-deficient mice were more active in the Porsolt's forced-swimming test and the tail-suspension test, and they did not become hyperactive after bulbectomy. Tac1 mutant mice were also less fearful in several animal models of anxiety. They were more active and less affected by the light conditions in the central area of the open-field arena; they showed more social interactions in an aversive environment, they were more active in the open areas of an elevated zero-maze, and they had a reduced latency to feed in the Thatcher-Britton conflict paradigm. These results demonstrate that tachykinins are powerful mediators of depression-like or anxiety-related behaviors in mice. The tachykinin system therefore may play an important role in the regulation of emotional states and the development of anxiety disorders and depression.