Involvement of 5-HT 1A and 5-HT 2 receptors of the dorsal periaqueductal gray in the regulation of the defensive behaviors generated by the elevated T-maze

Abstract

Previous studies have shown that serotonin plays an inhibitory role in escape behavior induced by the aversive stimulation of the dorsal periaqueductal gray matter (DPAG). This defensive behavior has been related to panic disorder. Serotonin injected into the DPAG also inhibits escape behavior generated by the elevated T-maze. Besides escape, this test also measures inhibitory avoidance, a behavior associated with generalized anxiety disorder. We presently evaluate the role of the 5-HT 1A, 5-HT 2A and 5-HT 2C receptors of the DPAG in the modulation of inhibitory avoidance and escape responses of rats submitted to the elevated T-maze. The results showed that intra-DPAG administration of the 5-HT 1A receptor antagonist WAY-100635 and of the preferential antagonists of 5-HT 2A and 5-HT 2C receptors, ketanserin and SDZ SER 082, respectively, did not change rat behavior in the elevated T-maze. Intra-DPAG injection of serotonin inhibited escape, an effect blocked by local injection of these three antagonists. Ketanserin and SDZ SER 082, but not WAY-100635 antagonized the effect of serotonin in facilitating inhibitory avoidance. Intra-DPAG injection of the 5-HT 1A agonist 8-OH-DPAT and of DOI, a preferential 5-HT 2A agonist, also inhibited escape, an effect antagonized by WAY-100635 and ketanserin, respectively. The results indicate that serotonin in the DPAG exerts a phasic regulatory control on inhibitory avoidance and escape behaviors in the elevated T-maze. 5-HT 1A and 5-HT 2C receptors in the DPAG play an opposite role in inhibitory avoidance: whereas activation of the former receptors inhibits the acquisition of this response, activation of the latter facilitates it. Both 5-HT 1A, 5-HT 2A and 5-HT 2C receptors seem to mediate the inhibitory action of serotonin on escape.