The head-twitch response in the least shrew (Cryptotis parva) is a 5-HT2- and not a 5-HT1C-mediated phenomenon.
Our initial studies suggested that the 5-HT2/1C agonist (+/-)-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 stimulation of 5-HT2 receptors. However, challenge studies revealed that these behaviors are produced via two different receptors (possibly 5-HT2 and 5-HT1C). Due to a lack of selective agents one cannot designate a particular response for the activation of a specific receptor. The purpose of the present study was to investigate such behaviors in the least shrew, which is more sensitive to (+/-)-DOI than rodents. IP injection of (+/-)-DOI in shrews produced a dose-dependent (bell-shaped) and time-dependent increase in the HTR frequency. The (+/-)-DOI-induced HTR was equipotently and completely attenuated by the 5-HT2/1C antagonists ketanserin and spiperone. The 5-HT1C antagonist with 5-HT2 agonist action, lisuride, also produced the HTR in a bell-shaped dose- and time-dependent fashion. Central injections of both (+/-)-DOI (0.2 microgram) and lisuride (0.5 microgram) also induced the behavior. Both peripheral and central administration of lisuride failed to produce the ESR. (+/-)-DOI significantly induced the ESR only at the highest dose tested (2.5 mg/kg, IP). Centrally administered (+/-)-DOI (0.2 microgram) produced more ESRs relative to vehicle controls; however, the difference did not attain significance. At low doses (0.31 and 0.63 mg/kg), (+/-)-DOI had no effect on locomotor activity, but it significantly attenuated the behavior at larger doses. Both low and high doses of lisuride increased the motor activity. Spiperone dose-dependently suppressed locomotion, whereas ketanserin had no effect. The present results suggest that the HTR is a 5-HT2 receptor-mediated event and changes in locomotor activity do not affect the induced HTR.
Darmani
N A
NA
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501.
Mock
O B
OB
Towns
L C
LC
Gerdes
C F
CF
D000662:Amphetamines / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007267:Injections; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D016548:Prosencephalon / Q000502:physiology; D011985:Receptors, Serotonin / Q000502:physiology*; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology; D012788:Shrews / Q000502:physiology*; D013997:Time Factors
D000662:Amphetamines; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C015952:4-iodo-2,5-dimethoxyphenylisopropylamine