THE HEAD-TWITCH RESPONSE IN THE LEAST SHREW (CRYPTOTIS-PARVA) IS A 5-HT2-MEDIATED AND NOT A 5-HT1C-MEDIATED PHENOMENON

Our initial studies suggested that the 5-HT2/1C (+/-)-1-(2,5-dimethoxy -4-iodophenyl-2-aminopropane [(+/-)-DOI] produces both the head-twitch response (HTR) and the ear-scratch response (ESR) in mice via stimula tion of 5-HT2 receptors. However, challenge studies revealed that thes e behaviors are produced via two different receptors (possibly 5-HT2 a nd 5-HT1C). Due to a lack of selective agents one cannot designate a p articular response for the activation of a specific receptor. The purp ose of the present study was to investigate such behaviors in the leas t shrew, which is more sensitive to (+/-)-DOI than rodents. IP injecti on of (+/-)-DOI in shrews produced a dose-dependent (bell-shaped) and time-dependent increase in the HTR frequency. The (+/-)-DOI-induced HT R was equipotently and completely attenuated by the 5-HT2/1C antagonis ts ketanserin and spiperone. The 5-HT1C antagonist with 5-HT2 agonist action, lisuride, also produced the HTR in a bell-shaped dose- and tim e-dependent fashion. Central injections of both (+/-)-DOI (0.2 mu g) a nd lisuride (0.5 mu g) also induced the behavior. Both peripheral and central administration of lisuride failed to produce the ESR. (+/-)-DO I significantly induced the ESR only at the highest dose tested (2.5 m g/kg, IF). Centrally administered (+/-)-DOI (0.2 mu g) produced more E SRs relative to vehicle controls; however, the difference did not atta in significance. At low doses (0.31 and 0.63 mg/kg), (+/-)-DOI had no effect on locomotor activity, but it significantly attenuated the beha vior at larger doses. Both low and high doses of lisuride increased th e motor activity. Spiperone dose-dependently suppressed locomotion, wh ereas ketanserin had no effect. The present results suggest that the H TR is a 5-HT2 receptor-mediated event and changes in locomotor activit y do not affect the induced HTR.