The histidine triad nucleotide-binding protein-1 gene (HINT1) is implicated in schizophrenia and in the behavioral effects of morphine and amphetamine. Because nicotine dependence (ND) is highly comorbid with schizophrenia and other substance abuse, we examined the association of HINT1 with ND. Association analyses from two independent samples show that HINT1 gene variants are associated with ND phenotypes. Furthermore, human postmortem mRNA expression shows that smoking status and genotype influence HINT1 expression in the brain. In animal studies, western blot analyses show an increase of HINT1 protein level in the mouse nucleus accumbens (NAc) after chronic nicotine exposure. This increase was reduced after treatment with the nicotinic-receptor antagonist mecamylamine, and 24 and 72 h after cessation of nicotine treatment. These results indicate a genetic association between HINT1 variants and ND, and indicate that nicotine-induced modulation of HINT1 level may be involved in mechanisms of excess smoking. The Pharmacogenomics Journal (2011) 11, 251-257; doi:10.1038/tpj.2010.41; published online 1 June 2010
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Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Chen, Qi
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Wang, Xu
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Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Wang, Xu
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O'Neill, Francis A.
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Walsh, Dermot
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Hlth Res Board, Dublin, IrelandVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Walsh, Dermot
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Kendler, Kenneth S.
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Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Kendler, Kenneth S.
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Chen, Xiangning
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Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
机构:
Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Chen, Qi
;
Wang, Xu
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机构:
Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Wang, Xu
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O'Neill, Francis A.
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Walsh, Dermot
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Hlth Res Board, Dublin, IrelandVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Walsh, Dermot
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Kendler, Kenneth S.
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机构:
Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Kendler, Kenneth S.
;
Chen, Xiangning
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机构:
Virginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA
Virginia Commonwealth Univ, Virginia Inst Psychiat & Behav Genet, Richmond, VA 23298 USAVirginia Commonwealth Univ, Dept Psychiat, Richmond, VA 23298 USA