Increased ethanol consumption despite taste aversion in mice with a human tryptophan hydroxylase 2 loss of function mutation.
Polymorphisms in the gene encoding the brain serotonin synthesis enzyme Tph2 have been identified in mental illnesses, with co-morbidity of substance use disorder. However, little is known about the impact of Tph2 gene variants on addiction. Mice expressing a human Tph2 loss of function variant were used to investigate consequences of aversive conditions on ethanol intake. Mice were familiarized either with ethanol or a solution containing both ethanol and the bittering agent quinine. Effect of familiarization to ethanol or an ethanol-quinine solution was then evaluated using a two-bottles preference test in Tph2-KI and control littermates. Mice from both genotypes displayed similar levels of ethanol consumption and quinine avoidance when habituated to ethanol alone. In contrast, addition of quinine to ethanol during the familiarization period resulted in a reduction of avoidance for the quinine-ethanol solution only in mutant mice. These results indicate that loss of function mutation in Tph2 results in greater motivation for ethanol consumption under aversive conditions and may confer enhanced sensitivity to alcohol use disorder.
École de Psychologie, Faculté des Sciences Sociales, Université Laval, Pavillon Félix-Antoine-Savard, 2325, Rue des Bibliothèques, Québec, Canada.
Francis
F
Lemay
École de Psychologie, Faculté des Sciences Sociales, Université Laval, Pavillon Félix-Antoine-Savard, 2325, Rue des Bibliothèques, Québec, Canada.
François Y
FY
Doré
Département de Psychiatrie et de Neurosciences, Faculté de Médecine, Université Laval, Pavillon Ferdinand-Vandry, 1050, Avenue de la Médecine, Québec, Canada. Electronic address: martin.beaulieu@crulrg.ulaval.ca.
Jean-Martin
JM
Beaulieu
D000428:Alcohol Drinking / Q000235:genetics / Q000523:psychology*; D000818:Animals; D001362:Avoidance Learning; D000431:Ethanol / Q000008:administration & dosage; D006801:Humans; D008817:Mice, Mutant Strains; D009042:Motivation; D009154:Mutation; D012646:Self Administration; D013649:Taste; D014364:Tryptophan; D014365:Tryptophan Hydroxylase / Q000235:genetics*
D000431:Ethanol; D014364:Tryptophan; C494784:TPH2 protein, human; D014365:Tryptophan Hydroxylase
Addiction; Alcohol; Polymorphism; Serotonin; Tryptophan hydroxylase 2