Antagonism of CRF(2) receptors produces anxiolytic behavior in animal models of anxiety.

Two pharmacologically distinct CRF receptors are distributed in different brain regions and peripheral tissues. Studies suggest that CRF(1) receptors play an important role in mediating the anxiety provoking effects of CRF. In contrast, far less functional information is available on CRF(2) receptors. Therefore, we conducted dose response studies using antisauvagine-30 (anti-SVG-30, 0-20 microg, 20-min pretreatment, i.c.v.), a potent CRF(2) peptide antagonist, and tested rats in three models of anxiety - the conditioned freezing, the elevated plus maze, and the defensive-withdrawal test. Anti-SVG-30 produced a significant dose-dependent reduction in conditioned freezing. In the elevated plus maze test, administration of anti-SVG-30 effectively increased the number of entries and time spent in the open arms. In the defensive-withdrawal test, anti-SVG-30 treatment facilitated exploratory activity in a large illuminated open field. Thus, in all three animal models, administration of anti-SVG-30 was consistent in producing an anxiolytic-like behavioral effect. In addition, a dose of anti-SVG-30 (10 microg) that produced anxiolytic-like behavior had no significant effects on locomotor activity measured in an automated activity box. This latter finding suggests that antagonism of CRF(2) receptors is not associated with a non-specific increase in behavioral movements. These results provide evidence that, in addition to CRF(1) receptors, CRF(2) receptors may play an important role in the mediation of anxiety behavior.