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.
Pranzatelli
M R
MR
Department of Neurology, College of Physicians and Surgeons, Columbia University, New York, NY 10032.
D000662:Amphetamines / Q000494:pharmacology*; D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D004146:Dioxanes / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology; D008297:Male; D008784:Methysergide / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000502:physiology*; D013141:Spiro Compounds / Q000494:pharmacology; D013239:Stereotyped Behavior / Q000187:drug effects*; D013469:Sulpiride / Q000494:pharmacology
D000662:Amphetamines; D004146:Dioxanes; D011985:Receptors, Serotonin; D013141:Spiro Compounds; D012701:Serotonin; D013469:Sulpiride; C018387:spiroxatrine; D006220:Haloperidol; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine; D008784:Methysergide