Median and dorsal raphe injections of the 5-HT1A agonist, 8-OH-DPAT, and the GABAA agonist, muscimol, increase voluntary ethanol intake in Wistar rats.
Low doses of the selective 5-HT1A agonist 8-OH-DPAT increase ethanol intake in a limited access paradigm following peripheral injection. This may be due to a reduction in 5-HT neurotransmission following activation of raphe somatodendritic autoreceptors. In order to test this hypothesis, and to determine the effects of selective reductions in raphe 5-HT activity, experiments examined the effects of injecting 8-OH-DPAT into the dorsal raphe (0, 0.02, 0.1, 1 and 2.5 micrograms) or the median raphe (0, 0.1, 1 and 5 micrograms) in rats trained to drink 12% ethanol for 40 min each day. The effects of the GABAA agonist, muscimol, on ethanol intake were also examined. Ethanol intake was increased at the highest dose of 8-OH-DPAT following injection into either site, with no change in water intake. Thus, the effects of 8-OH-DPAT are selective for ethanol. The selective 5-HT1A antagonist, (+)-WAY100135 (0.3, 1 and 3 mg/kg), blocked the effect of 8-OH-DPAT, showing that activation of 5-HT1A receptors underlies the ethanol drinking induced by 8-OH-DPAT. These results are consistent with the idea that reduced 5-HT function increases ethanol intake. Several behavioral mechanisms for this effect are discussed. Muscimol (50-100 ng) also increased ethanol drinking. Following injection into the median raphe, muscimol also stimulated water intake. These effects are probably due to non-specific behavioural activation induced by this treatment. However, the effect of muscimol in the dorsal raphe was specific for ethanol since water intake was not altered.(ABSTRACT TRUNCATED AT 250 WORDS)
Tomkins
D M
DM
Addiction Research Foundation, Toronto, Ontario, Canada.
Sellers
E M
EM
Fletcher
P J
PJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000008:administration & dosage / Q000494:pharmacology*; D000428:Alcohol Drinking; D000818:Animals; D058785:GABA-A Receptor Agonists; D008297:Male; D009118:Muscimol / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage / Q000494:pharmacology*
D058785:GABA-A Receptor Agonists; D010879:Piperazines; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; C081293:WAY 100135; D009118:Muscimol; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin