Suppression of alcohol and saccharin preference in rats by a novel Ca2+ channel inhibitor, Goe 5438
- 25 Downloads
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 µmol/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 µmol/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. Additionally, this particular Ca2+ channel inhibitor appears to have mild anorectic properties which may be conducive to acute suppression of alcohol intake.
Key wordsGoe 5438 Ethanol Preference Ca2+ channel inhibitors Saccharin consumption Food intake Drinking behavior
Unable to display preview. Download preview PDF.
- Fadda F, Mosca E, Colombo G, Gessa GL (1990) Alcohol preferring rats: genetic sensitivity to alcohol-induced stimulation of dopamine metabolism. Physiol Behav 47:727–729Google Scholar
- Fadda F, Colombo G, Marchei MF, Gessa GL (1991) Inhibition of ethanol intake by a calcium-channel blocker, isradipine, in ethanol-preferring rats. Alcohol Clin Exp Res 15:314Google Scholar
- Hofmann HP, Raschack M, Unger L (1989) (S)-Emopamil, a novel calcium and serotonin antagonist for the treatment of cerebrovascular disorders. Drug Res 39:304–308Google Scholar
- Li T-K, Lumeng L, McBride WJ, Waller WB (1981) Indiana selection studies on alcohol-related behaviors. In: McClearn GE, Deitrich RA, Irvin VG (eds) Development of animal models as pharmacogenetic tools. NIAAA Research Monograph-6. Rockville, pp 171–191Google Scholar
- Mello NK (1983) A behavioral analysis of the reinforcing properties of alcohol and other drugs in man. In: Kissin B, Begleiter H (eds) The pathogenesis of alcoholism, biological factors, vol 7. Plenum Press, New York, pp 133–198Google Scholar
- Osswald H, Weinheimer G, Dooley DJ, Preuner J, Kleinschroth J, Mannhardt K, Hartenstein J, Satzinger G (1986) Smooth muscle relaxing and membrane binding characteristic of a new naphthyridine derivative Goe 5438 (CI-951). Naunyn-Schmiedeberg's Arch Pharmacol 334 [suppl]:R28Google Scholar
- Rezazadeh SM, Woodward JJ, Leslie SW (1980) Fura-2 measurement of cytostolic free calcium in rat brain cortical synaptosomes and the influence of ethanol. Alcohol 6:341–345Google Scholar
- Rezvani AH, Pucilowski O, O'Brien R, Janowsky DS (1991b) Attenuation of alcohol preference by (S)-emopamil, a novel Ca++, antagonist in the rat. NCARA 15th Annual Symposium on Alcoholism: The Search for the Sources. Raleigh, NC (abstract)Google Scholar
- Rezvani AH, Pucilowski O, Janowsky DS (1991c) Effects of different Ca++ channel antagonists on alcohol preference in alcohol preferring rats. Alcohol Clin Exp Res 15:314Google Scholar
- Tallarida RJ, Murray RB (1987) Manual of pharmacologic calculations with computer programs. Springer-Verlag, New YorkGoogle Scholar
- Waller MB, McBride WJ, Gatto GJ, Li T-K (1984) Intragastric self-administration of ethanol by ethanol-preferring and -non-preferring lines of rats. Science 225:78–80Google Scholar