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 μg, 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 μg) 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.
Brain Research – Elsevier
Published: Jun 1, 2001
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