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BDNF Val66Met genotype is associated with drug-seeking phenotypes in heroin-dependent individuals: a pilot study

Authors

  • Mark K. Greenwald,

    Corresponding author
    1. Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
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  • Caren L. Steinmiller,

    1. Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
    2. Department of Pharmacology, College of Pharmacy and Pharmaceutical Sciences, University of Toledo, Toledo, OH, USA
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  • Elzbieta Śliwerska,

    1. Department of Psychiatry, and Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA
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  • Leslie Lundahl,

    1. Substance Abuse Research Division, Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA
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  • Margit Burmeister

    1. Department of Psychiatry, and Molecular & Behavioral Neuroscience Institute, University of Michigan, Ann Arbor, MI, USA
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Mark Greenwald, Department of Psychiatry and Behavioral Neurosciences, Substance Abuse Research Division, 2761 East Jefferson Ave., Detroit, MI 48207, USA. E-mail: mgreen@med.wayne.edu

ABSTRACT

Brain-derived neurotrophic factor (BDNF) Val66Met genotype has been associated with neurobehavioral deficits. To examine its relevance for addiction, we examined BDNF genotype differences in drug-seeking behavior. Heroin-dependent volunteers (n = 128) completed an interview that assessed past-month naturalistic drug-seeking/use behaviors. In African Americans (n = 74), the Met allele was uncommon (carrier frequency 6.8%); thus, analyses focused on European Americans (n = 54), in whom the Met allele was common (carrier frequency 37.0%). In their natural setting, Met carriers (n = 20) reported more time- and cost-intensive heroin-seeking and more cigarette use than Val homozygotes (n = 34). BDNF Val66Met genotype predicted 18.4% of variance in ‘weekly heroin investment’ (purchasing time × amount × frequency). These data suggest that the BDNF Met allele may confer a ‘preferred drug-invested’ phenotype, resistant to moderating effects of higher drug prices and non-drug reinforcement. These preliminary hypothesis-generating findings require replication, but are consistent with pre-clinical data that demonstrate neurotrophic influence in drug reinforcement. Whether this genotype is relevant to other abused substances besides opioids or nicotine, or treatment response, remains to be determined.

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