The reduction in alcohol intake by the 5-HT1A agonist 8-OH DPAT and its attenuation by the α2 adrenergic antagonist idazoxan correlates with blood glucose levels |
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Authors: | Larry A. Grupp Vicky Lau Stephen Harding |
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Affiliation: | (1) Biobehavioral Research Department, Addiction Research Foundation of Ontario, Toronto, Ontario, Canada M5S 2S1, CA;(2) Department of Pharmacology, Medical Sciences Building, Room 4311, University of Toronto, Toronto, Canada M5S 1A8 Fax (+1) 416/978-6395, CA |
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Abstract: | Serotonergic agents in general and the 5-HT1A agonist 8-OH DPAT in particular, reduce alcohol intake in rats and primates but the mechanism of this effect is not known. Previous studies have shown a correlation between alcohol consumption and the propensity to consume sweet substances. Indeed, certain biochemical events accompanying glucose utilization have been proposed as satiety signals in the control of feeding. Since 8-OH DPAT produces hyperglycemia, we tested the hypothesis that its effect on alcohol intake may be partly mediated through an increase blood glucose. Male Wistar rats were trained to drink a bout of 6% (w/v) alcohol using the limited access procedure which offers a daily 40-min access to alcohol and water. On consecutive test trial days separated by intervening non-drug days, the amount of alcohol consumed (1 g/kg on intervening days) was measured following the administration of 8-OH DPAT (150 μg/kg 10 min prior to drinking) alone or in combination with the prior (20 min) injection of idazoxan (2 mg/kg), an alpha-2 adrenoceptor antagonist with hypoglycemic properties. Idazoxan attenuated the hyperglycemic effect of 8-OH DPAT and completely reversed 8-OH DPAT’s inhibitory effect on alcohol intake. Idazoxan alone produced a mild hypoglycemia and stimulated alcohol intake. These results support a role for glucoregulatory processes in serotonergically-mediated changes in alcohol consumption. Received: 22 November 1996 / Final version: 25 March 1997 |
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Keywords: | Alcohol intake 8-OH DPAT Idazoxan 5-HT1A agonist Alpha-2 adrenoceptor antagonist Blood glucose Serotonin |
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