Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor, Goe 5438.
The effect of the novel 1,4-dihydronaphthyridine Ca2+ channel inhibitor Goe 5438 (CI-951) on voluntary ethanol consumption was examined in selectively bred alcohol-preferring (P) rats in a free choice two bottle preference test versus water. Intraperitoneally injected Goe 5438 dose-dependently (5, 10 or 20 mumol/kg, twice daily) inhibited ethanol and increased water intake over the 24 h period (injection day). The drug decreased ethanol preference, originally above 90%, by 6%, 19% and 45% at respective doses, on the injection day. That inhibitory effect of the highest dose of Goe 5438 on ethanol preference remained significant also on days 2 and 3 after injections (-51% and -18%, respectively). Goe 5438, in the highest dose, also tended to decrease granulated chow consumption during the injection day only. To further test whether the inhibition of ethanol preference is secondary to decrease in reinforcing properties of ethanol and not due to interference with satiety mechanisms, we compared the effect of two higher doses (10 and 20 mumol/kg, intraperitoneally, twice daily) of Goe 5438 on spontaneous preference for a non-caloric 0.04% saccharin solution in Sprague-Dawley rats. We observed a dose-dependent suppression of preference (by 44% and 58%, respectively) during the injection day, but not the subsequent 24 h period. However, Goe 5438 also significantly alleviated food pellet intake on the injection day. In conclusion, Goe 5438 produces potent and long-lasting inhibition of voluntary ethanol consumption, which may be secondary to attenuation of reinforcing properties of ethanol.(ABSTRACT TRUNCATED AT 250 WORDS)
Pucilowski
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Skipper Bowles Center for Alcohol Studies, University of North Carolina, Chapel Hill, School of Medicine 27599-7175.
Rezvani
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Janowsky
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D000428:Alcohol Drinking / Q000523:psychology*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004435:Eating / Q000187:drug effects; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D009287:Naphthyridines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012439:Saccharin / Q000494:pharmacology*
D001067:Appetite Depressants; D002121:Calcium Channel Blockers; D009287:Naphthyridines; C056825:Goe 5438; D000431:Ethanol; D012439:Saccharin