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Abstract

Evidence for central alpha-2 adrenoceptors, not imidazoline binding sites, mediating the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists.

M J Durcan, R G Lister and M Linnoila
Journal of Pharmacology and Experimental Therapeutics August 1991, 258 (2) 576-582;
M J Durcan
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R G Lister
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M Linnoila
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Abstract

The role of central adrenoceptors in the ethanol-attenuating effects of alpha-2 adrenoceptor blockers was investigated in mice; the centrally active antagonist atipamezole was compared with L 659,066, which penetrates the brain poorly. L 659,066 (1-10 mg/kg) had no effect on the hypothermia induced by ethanol (2 g/kg) or ethanol ataxia (2.4 g/kg), whereas atipamezole (1 mg/kg) significantly attenuated both ethanol-induced hypothermia and ataxia. Atipamezole (1-3 mg/kg) significantly attenuated the ethanol-induced reduction in exploratory head-dipping in a holeboard test whereas L 659,066 was only effective at a dose of 1 mg/kg, higher doses (3 and 10 mg/kg) and a lower dose (0.3 mg/kg) were ineffective. Atipamezole was without effect on ethanol's locomotor stimulant effect in the holeboard but L 659,066 attenuated this effect at doses less than 3 mg/kg Many alpha-2 adrenoceptor ligands also have affinity for nonadrenergic imidazoline-binding sites. The role these sites may play in attenuating ethanol's effects was investigated by comparing RX 821002 (methoxy idazoxan), which has little or no affinity for imidazoline-binding sites with atipamezole. Both atipamezo 1 e (1 mg/kg) and RX 821002 (0.06-0.2 mg/kg) significantly attenuated ethanol-induced hypothermia, ataxia and reduction in head-dipping, but were without effect on ethanol-induced locomotor stimulation. These results suggest that nonadrenergic imidazoline-binding sites are not implicated in the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 258, Issue 2
1 Aug 1991
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Abstract

Evidence for central alpha-2 adrenoceptors, not imidazoline binding sites, mediating the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists.

M J Durcan, R G Lister and M Linnoila
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 576-582;

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Abstract

Evidence for central alpha-2 adrenoceptors, not imidazoline binding sites, mediating the ethanol-attenuating properties of alpha-2 adrenoceptor antagonists.

M J Durcan, R G Lister and M Linnoila
Journal of Pharmacology and Experimental Therapeutics August 1, 1991, 258 (2) 576-582;
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