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Additive Reduction of Alcohol Drinking by 5‐HT 1A Antagonist WAY 100635 and Serotonin Uptake Blocker Fluoxetine in Alcohol‐Preferring P Rats
Author(s) -
Zhou Feng C.,
McKinzie David L,
Patel Tushar D.,
Lumeng Lawrence,
Li TingKai
Publication year - 1998
Publication title -
alcoholism: clinical and experimental research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.267
H-Index - 153
eISSN - 1530-0277
pISSN - 0145-6008
DOI - 10.1111/j.1530-0277.1998.tb03648.x
Subject(s) - antagonist , serotonin , ethanol , chemistry , endocrinology , 5 ht receptor , alcohol , medicine , fluoxetine , pharmacology , receptor , biochemistry
We found previously that alcohol‐preferring (P) rats have fewer serotonin (5‐HT) neurons and fibers in key brain regions than alcoholnonpreferring (NP) rats. Because 5‐HT uptake blockers increase synaptic 5‐HT content and 5‐HT 1A receptor antagonists increase 5‐HT release by disinhibiting 5‐HT autoinnervation, in the present study, our intent was to determine whether increased synaptic 5‐HT content and/or 5‐HT release in P rats would effectively reduce alcohol consumption. In experiment 1, the 5‐HT antagonist WAY 100635 (WAY) was tested on adult female P rats maintained on 24‐hr free‐choice access to ethanol (10% v/v) and water. Twice daily doses of WAY (0.05, 0.1, 0.5, and 1.0 mg/kg, subcutaneously) were administered to each rat in a counterbalanced order. Baseline ethanol intake, derived from the mean ethanol intakes of the three previous non‐drug days, was approximately 8 g/kg/day. Results indicated that 0.05,0.1, and 0.5 mg/kg doses of WAY reduced 24‐hr ethanol drinking by 25‐30% ( p < 0.01) without affecting 24‐hr water intake or body weight In the second experiment, the effects of WAY (0.5 mg/kg), fluoxetine (1.0 mg/kg), or a combination of both were tested in another group of female P rats. WAY and fluoxetine, each alone, reduced ethanol drinking by around 20% and, when combined, decreased ethanol intake by 50%, whereas the body weight and the total fluid intake were not significantly affected. Taken together, these results indicate that both fluoxetine and WAY preferentially reduce ethanol drinking in the P line of rats and, when administered together, reduce ethanol intake in an additive manner. It is proposed that coadministration of these two compounds with distinct mechanisms of action may be a new strategy for reducing alcohol intake.