A null mutation of the serotonin 6 receptor alters acute responses to ethanol

The anatomical distribution and pharmacology of serotonin 6 receptors (5-HT6Rs) implicate them as contributors to the serotonergic regulation of complex behavior. To complement the limited range of pharmacological tools available to examine 5-HT6R function, we have generated a mouse line bearing a constitutive null mutation of the 5-HT6R gene. No perturbations of baseline behavior were noted in a wide array of assays pertinent to multiple neurobehavioral processes. However, 5-HT6R mutant mice demonstrated reduced responses to the ataxic and sedative effects of ethanol. No differences in ethanol metabolism were evident between wild-type and 5-HT6R mutant mice. These findings implicate 5-HT6Rs in the serotonergic modulation of responses to ethanol.