The reduction in alcohol intake by the 5-HT1A agonist 8-OH DPAT and its attenuation by the alpha 2 adrenergic antagonist idazoxan correlates with blood glucose levels.
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 micrograms/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.
Grupp
L A
LA
Biobehavioral Research Department, Addiction Research Foundation of Ontario, Toronto, Canada.
Lau
V
V
Harding
S
S
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology*; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D000431:Ethanol / Q000008:administration & dosage*; D005247:Feeding Behavior / Q000187:drug effects* / Q000502:physiology; D019329:Idazoxan / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*
D000317:Adrenergic alpha-Antagonists; D001786:Blood Glucose; D017366:Serotonin Receptor Agonists; D000431:Ethanol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; D019329:Idazoxan