Activation of 5-HT 2C receptors in the dorsal periaqueductal gray increases antinociception in mice exposed to the elevated plus-maze

摘要

Several findings have pointed to the role of the dorsal periaqueductal gray (dPAG) serotonin 5-HT 1A and 5-HT 2A-C receptor subtypes in the modulation of defensive behavior in animals exposed to the elevated plus-maze (EPM). Besides displaying anxiety-like behavior, rodents also exhibit antinociception in the EPM. This study investigated the effects of intra-dPAG injections of 5-HT 1A and 5-HT 2B/2C receptor ligands on EPM-induced antinociception in mice. Male Swiss mice received 0.1μl intra-dPAG injections of vehicle, 5.6 and 10nmol of 8-OHDPAT, a 5-HT 1A receptor agonist (Experiment 1), or 0.01, 0.03 and 0.1nmol of mCPP, a 5-HT 2B/2C receptor agonist (Experiment 2). Five minutes later, each mouse received an intraperitoneal injection of 0.6% acetic acid (0.1ml/10g body weight; nociceptive stimulus) and was individually confined in the open (OA) or enclosed (EA) arms of the EPM for 5min, during which the number of abdominal writhes induced by the acetic acid was recorded. While intra-dPAG injection of 8-OHDPAT did not change open-arm antinociception (OAA), mCPP (0.01nmol) enhanced it. Combined injections of ketanserin (10nmol/0.1μl), a 5-HT 2A/2C receptor antagonist, and 0.01nmol of mCPP (Experiment 3), selectively and completely blocked the OAA enhancement induced by mCPP. Although intra-dPAG injection of mCPP (0.01nmol) also produced antinociception in EA-confined mice (Experiment 2), this effect was not confirmed in Experiment 3. Moreover, no other compound changed the nociceptive response in EA-confined animals. These results suggest that the 5-HT 2C receptors located within the PAG play a role in this type of environmentally induced pain inhibition in mice.