Alcohol intake after serotonin transporter inactivation in mice.

Knock-out mice lacking the serotonin transporter [5-hydroxytryptamine transporter (5-HTT)] were used to assess the influence of 5-HT re-uptake on ethanol consumption. Under a free-choice paradigm, alcohol intake was lower in mutant than in wild-type mice, and pharmacological blockade of 5-HTT by fluoxetine reduced alcohol intake in wild-type mice only. These data confirm the inhibitory effect of 5-HTT inactivation on ethanol intake.

Reappraisal of the serotonin 5-HT(1B) receptor gene in alcoholism: of mice and men.

Because pharmacological and genetic data supported the idea that serotonin receptors of the 5-HT(1B) type can play a modulatory role in alcohol consumption in both human and rodents, the 5-HT(1B) receptor gene is considered as a candidate gene for alcohol dependence. However, contradictory results have been reported as a positive association between alcohol dependence, and either the 861C or the 861G allele of the G861C polymorphism of the 5-HT(1B) receptor gene can be found in the literature. Further investigations in a population of 136 male alcoholics compared with 72 male control subjects demonstrated that none of these alleles was actually associated with alcohol dependence. In addition, in contrast with previous results of the literature, ethanol intake under free choice conditions (i.e., ethanol solution vs. water) was found to be similar in 5-HT(1B)-/- knock mice and paired wild-type controls. The 5-HT(1B) receptor gene may thus not be a key component in the genetic background underlying alcohol dependence in human and alcohol preference in rodents, although these results should be considered as preliminary according to the small size of our sample.