Interactions of alpha 2-adrenoceptor antagonists with medetomidine and with ethanol in a holeboard test.
The effects of two selective alpha 2-adrenoceptor agonists (clonidine and medetomidine) and antagonists (atipamezole and idazoxan) were examined in the holeboard test. The interactions of the two antagonists with ethanol were also investigated. Atipamezole (0.1-3.0 mg/kg) and idazoxan (0.01-0.3 mg/kg) were without effect on either directed exploration or locomotor activity in the holeboard test, whereas clonidine (0.003-0.1 mg/kg) and medetomedine (0.003-0.1 mg/kg) were sedative. Atipamezole (1-3 mg/kg) and idazoxan (0.3-1.0 mg/kg) reversed the behavioral effects of 0.1 mg/kg of medetomidine. When administered with ethanol (2 g/kg), atipamezole (1-3 mg/kg) showed a significant antagonism of the ethanol-induced reduction in exploratory head-dipping: no change in the locomotor stimulant properties of ethanol was seen. A similar trend was seen for exploration after a combination of idazoxan (1-3 mg/kg) with 2 g/kg ethanol; however, the 3 mg/kg dose attenuated the locomotor stimulant effect. Both antagonists caused a dose-related reduction in the increase in head-dipping seen after administration of 1 g/kg of ethanol, without any effect on the locomotor stimulant effect of this dose. These results suggest mediation of alpha 2-adrenoceptors in some of the behavioral effects of ethanol.
Durcan
M J
MJ
Laboratory of Clinical Studies, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Maryland 20892.
Lister
R G
RG
Linnoila
M
M
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D004146:Dioxanes / Q000494:pharmacology; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D019329:Idazoxan; D007093:Imidazoles / Q000494:pharmacology*; D008297:Male; D020926:Medetomidine; D051379:Mice
D000316:Adrenergic alpha-Agonists; D000317:Adrenergic alpha-Antagonists; D004146:Dioxanes; D007093:Imidazoles; C050701:atipamezole; D000431:Ethanol; D003000:Clonidine; D020926:Medetomidine; D019329:Idazoxan