Behavioral responses to stress following central and peripheral injection of the 5-HT(2) agonist DOI

Evidence suggests that serotonin (5-HT) systems are involved in the regulation of an organism's response to stress. Experiments were conducted to evaluate the possibility that central (20, 100, or 200 microg icv), peripheral (0.1, 0.5, or 1.0 mg/kg sc), or combined central (200 microg) plus peripheral (0.1 mg/kg) injections of the selective 5-HT(2) agonist (+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane HCl (DOI) would alter behavioral responses to stress in rats. Animals were evaluated during tail pinch stress, in an open field, and on a rotarod task. Across the three modes of administration (icv, sc, icv+sc), DOI resulted in a dose-related decrease in five of seven classes of behaviors observed during tail pinch. This reduction was most pronounced following subcutaneous injections, but occurred following intracerebroventricular and combined subcutaneous and intracerebroventricular injections as well. An additive effect of combined intracerebroventricular and subcutaneous administration was suggested by the fact that doses which were ineffective when given singly by these two routes resulted in a reduction in stress-evoked behavior when given together. Reduced responding seemed not to be attributable to general motoric impairment as DOI did not affect locomotion, grooming, or rotarod performance. The results suggest that activation of 5-HT(2) receptors produces an anxiolytic effect in rats subjected to acute tail pinch stress.