Evidence for involvement of 5-HT2 and 5-HT1C receptors in the behavioral effects of the 5-HT agonist 1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2 (DOI)

DOI (1-(2,5-dimethoxy-4-iodophenyl aminopropane)-2) has recently been suggested as a selective 5-HT2 receptor agonist, but its behavioral effects have not been previously reported. In naive rats, DOI induced dose-dependent shaking behavior, the novel behavior 'skin jerks' (paraspinal muscle contractions), and forepaw tapping of the 'serotonin syndrome'. These behaviors had a similar dose-response and time course and were blocked by the 5-HT2/5-HT1C antagonists mianserin, ritanserin, and methysergide. Skin jerks, unlike other behaviors, were not blocked by 1-propranolol or phenoxybenzamine, drugs with little activity at 5-HT2/5-HT1C sites. Differences in the pharmacology and neuroanatomy between skin jerks and shaking behavior suggest that the 5-HT1C receptor may participate in skin jerks and the 5-HT2 receptor in shaking behavior, but drug coaffinities for 5-HT2 and 5-HT1C receptors require further investigation.