Attenuation of some alcohol-induced mood changes and the desire to drink by 5-HT3 receptor blockade: a preliminary study in healthy male volunteers

Abstract

We studied the effect of the 5-HT3 receptor antagonist ondansetron (4 mg orally) on some of the psychological effects of a small dose of alcohol (580 ml of 3.6% alcohol content by volume of lager) in 16 healthy male volunteers using a double-blind placebo controlled, Latin Square cross-over design. Pretreatment with ondansetron significantly attenuated several of the subjective pleasurable effects of alcohol, and also decreased the subjective desire to drink. These findings are consistent with preclinical studies suggesting that the reinforcing properties of alcohol may be attenuated by 5-HT3 receptor blockade.

Update on neuropharmacological treatments for alcoholism: Scientific basis and clinical findings

“…Second, 5-HT 3 receptor antagonists inhibit DiMe-C7 (a neurokinin)-induced hyperlocomotion, which also is reduced by the dopamine antagonist, fluphenazine [218,219]. Third, 5-HT 3 receptor antagonists reduce ethanol consumption in several animal models and across different species [191,213,[220][221][222][223][224][225][226][227][228] cf. [229].…”

“…In two distinct experiments, Johnson and Cowen [214] and Johnson et al [224] showed that ondansetron pretreatment attenuated lowdose alcohol-induced positive subjective effects (including the desire to drink). Swift et al [230], using much higher alcohol and ondansetron doses, also discovered that ondansetron compared with placebo pretreatment reduced alcohol preference; however, a mixture of both stimulant and sedative interactions between ondansetron and alcohol also was observed.…”

A Mutation in Transmembrane Domain II of the 5-Hydroxytryptamine3A Receptor Stabilizes Channel Opening and Alters Alcohol Modulatory Actions

“…The most well documented actions of 5-HT 3 receptors are to alter gastrointestinal motility and to regulate the vomiting reflex (Aapro, 1991). Moreover, the 5-HT 3 receptor has been implicated in altering the voluntary intake of ethanol in humans (Johnson et al, 1993) and rodents (Knapp and Pohorecky, 1992;Hodge et al, 1993).The 5-HT 3 receptor is modulated by pharmacologically relevant concentrations of n-chain alcohols and anesthetics. Alcohols and volatile anesthetics, in the presence of low 5-HT concentrations, potentiate native and heterologously expressed 5-HT 3 receptors (Lovinger and White, 1991;Machu and Harris, 1994).…”

Pharmacogenetics - A Treatment Strategy for Alcoholism

“…Human laboratory studies have demonstrated that ondansetron decreases alcohol preference and desire to drink (Johnson et al, 1993). The efficacy of ondansetron in reducing drinking behavior has also been reported in Clinical trials, especially in drinkers with early onset alcoholism .…”