Effects of selective serotonin2 ligands on behaviors evoked by stress in the rat

Serotonin (5-HT) has been implicated in the regulation of the stress response. Two experiments were conducted to investigate the possibility that the 5-HT2A, 2C agonist DOI would reduce behavioral responsiveness to stress, and that selective blockade of one or both of these receptor subtypes would reverse this effect. Stressors employed were mild tail pinch and an illuminated open field. In Experiment 1 DOI (0.1, 0.5, 1.0 mg/kg, s.c.) was found to decrease stress-evoked oral behavior directed at food and to increase rearing behavior in a dose-dependent fashion. Neither of these effects was reversed by spiperone (5-HT2A antagonist) or SDZ SER-082 (5-HT2C antagonist). DOI also increased the frequency of head shaking. This effect was reversed by SDZ SER-082. In Experiment 2 DOI was injected singly or in combination with ketanserin (5-HT2A, 2C antagonist). DOI decreased tail pinch-evoked oral behavior directed at food, the amount of food eaten, and increased vocalization. In the open field DOI decreased rearing, increased the number of head shakes, and increased the incidence of flat body posture. While ketanserin alone (0.5, 2.5, 5.0 mg/kg) had no effect on any behavioral measure, coadministration of ketanserin (5.0 mg/kg) with DOI (0.5 and 1.0 mg/kg) significantly blocked the effects of DOI on oral behavior directed at food, eating, rearing, head shaking, and flat body posture. It is concluded that the observed effects of DOI on behaviors evoked by stress were mediated by activation of both 5-HT2A and 5-HT2C receptors.