Comparison of yohimbine, mianserin, chlorpromazine and prazosin as antagonists of the suppressant effect of clonidine on operant behavior
Dwoskin, L.P.; Sparber, S.B.
Journal of Pharmacology and Experimental Therapeutics 226(1): 57-64
1983
ISSN/ISBN: 0022-3565 PMID: 6864550 Document Number: 210732
Male Sprague-Dawley rats were trained to respond on a fixed-ratio schedule in which every 15th response produced a pellet of food. Clonidine (1-300 .mu.g/kg i.p.) , administered 30 min before the sessions, produced a dose-dependent suppression of operant responding. The ED50 for the suppression of operant responding induced by clonidine was 25 .mu.g/kg. Coadministration of low, behaviorally inactive doses of yohimbine (0.25-1.0 mg/kg) antagonized the operant suppression produced by clonidine (15-300 .mu.g/kg). After yohimbine (1.0 mg/kg), the ED50 for the suppression of responding induced by clonidine was increased .apprx. 4-fold to 115 .mu.g/kg. Higher doses of yohimbine (2.5-5.0 mg/kg) produced behavioral suppression when administered alone. The suppression of operant responding produced by cloidine apparently results, at least in part, from a selective .alpha.2-receptor stimulation. The behavioral suppression produced by the higher doses of clonidine (90 and 300 .mu.g/kg) which was not blocked by yohimbine may be the result of an additional action at receptor sites other than the .alpha.2-receptor. Coadministration of mianserin (1.0-35.0 mg/kg), chlorpromazine (0.5-2.5 mg/kg) or prazosin (0.01-0.5 mg/kg) failed to antagonize the suppressant effect of clonidine. The inability of chlorpromazine or prazosin to antagonize the behavioral suppression produced by clonidine indicates that clonidine is not acting solely or primarily through stimulation of the .alpha.1-receptor to produce some of its behavioral effect at high doses. The inability of mianserin to antagonize the suppression of behavior produced by clonidine indicates that mianserin is probably not an .alpha.2-antagonist or a yohimbine-like drug at the doses employed. Because low doses of clonidine (1-15 .mu.g/kg) were unable to antagonize the suppression of behavior produced by yohimbine (5 mg/kg), it appears that yohimbine too has other actions at higher doses.