Pharmacological characterization of ear-scratch response in mice as a behavioral model for selective 5-HT2-receptor agonists and evidence for 5-HT1B- and 5-HT2-receptor interactions.
(+/-) 1-(2,5-Dimethoxy-4-iodophenyl)-2-aminopropane [(+/-)-DOI], a phenylisopropylamine hallucinogen, is a 5-HT2-receptor agonist. The drug induced a dose-dependent increase in ear-scratch response (ESR) in mice, and the R(-)-isomer was more than 6 times as potent as its S(+)-enantiomer. The induced behavior was potently inhibited by selective 5-HT2-receptor antagonists such as ketanserin and spiperone. The (+/-)-DOI-induced ESR is also inhibited by stimulation of 5-HT1-receptors and the inhibition seems to be through a 5-HT1B-receptor mechanism. Thus, taken together, the present investigation indicates that ESR is due to selective stimulation of 5-HT2-receptors and that simultaneous costimulation of 5-HT1B-receptors inhibits the induced behavior. The study further suggests that the inability of the indolealkylamine hallucinogens to induce ESR is due to simultaneous excitation of 5-HT1B-receptors which are inhibitory to induction of ESR. Moreover, the data suggest possible inhibitory control mechanisms through 5-HT1-receptor subtypes to provide a damping mechanism to reduce excessive 5-HT2-receptor excitation due to exogenous drug stimulation or pathological conditions.
Darmani
N A
NA
Department of Pharmacology/Toxicology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298.
Martin
B R
BR
Pandey
U
U
Glennon
R A
RA
D000588:Amines / Q000494:pharmacology; D000662:Amphetamines / Q000037:antagonists & inhibitors; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006213:Hallucinogens / Q000494:pharmacology*; D051379:Mice; D008813:Mice, Inbred ICR; D011985:Receptors, Serotonin / Q000145:classification / Q000187:drug effects* / Q000502:physiology; D012702:Serotonin Antagonists / Q000494:pharmacology
D000588:Amines; D000662:Amphetamines; D006213:Hallucinogens; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine