Additive reduction of alcohol drinking by 5-HT(1A) antagonist WAY 100635 and serotonin uptake blocker fluoxetine in alcohol-preferring P rats

Feng Zhou, David L. McKinzie, Tushar D. Patel, Lawrence Lumeng, Ting Kai Li

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

We found previously that alcohol-preferring (P) rats have fewer serotonin (5-HT) neurons and fibers in key brain regions than alcohol- nonpreferring (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.

Original languageEnglish
Pages (from-to)266-269
Number of pages4
JournalAlcoholism: Clinical and Experimental Research
Volume22
Issue number1
StatePublished - Feb 1998

Fingerprint

Serotonin Antagonists
Fluoxetine
Alcohol Drinking
Rats
Serotonin
Ethanol
Alcohols
Drinking
Body Weight
Receptor, Serotonin, 5-HT1A
N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
Water
Neurons
Brain
Experiments
Fluids
Fibers

Keywords

  • Alcohol- preferring rats
  • Autoreceptor
  • Serotonin receptors
  • Serotonin transporter
  • SSRI

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Toxicology

Cite this

Additive reduction of alcohol drinking by 5-HT(1A) antagonist WAY 100635 and serotonin uptake blocker fluoxetine in alcohol-preferring P rats. / Zhou, Feng; McKinzie, David L.; Patel, Tushar D.; Lumeng, Lawrence; Li, Ting Kai.

In: Alcoholism: Clinical and Experimental Research, Vol. 22, No. 1, 02.1998, p. 266-269.

Research output: Contribution to journalArticle

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abstract = "We found previously that alcohol-preferring (P) rats have fewer serotonin (5-HT) neurons and fibers in key brain regions than alcohol- nonpreferring (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.",
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