Stress-induced cigarette craving: effects of the DRD2 TaqI RFLP and SLC6A3 VNTR polymorphisms.
Animal models have long implicated dopamine in stress-induced craving for a variety of addictive substances. However, translational studies of dopamine, stress and craving in humans are lacking. Based on the animal literature, this study's objective was to test the hypothesis that cigarette smokers carrying specific variants in dopamine-related genes would have heightened levels of cigarette craving following exposure to a laboratory stressor. Cigarette craving induced by controlled exposure to a laboratory stressor was assessed in healthy adult smokers (n=108) recruited by advertisement. Significantly stronger stress-induced cigarette craving was found for individuals carrying either the DRD2 (D2 dopamine receptor gene) A1, or the SLC6A3 (dopamine transporter gene) nine-repeat allelic variants. Stress-induced craving was markedly higher for those carrying both alleles, compared to those with neither, consistent with the separate biological pathways involved (receptor, transporter). Findings provide strong support for the possibility that dopamine involvement in stress-induced craving well established in animal models also applies to humans, and suggest a potential genetic risk factor for persistent smoking behavior.
Erblich
J
J
Derald H Ruttenberg Cancer Center, Mount Sinai School of Medicine, One Gustave L Levy Place, New York, NY 10029, USA. joel.erblich@mssm.edu
Lerman
C
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Self
D W
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Diaz
G A
GA
Bovbjerg
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DH
D000328:Adult; D000704:Analysis of Variance; D016739:Behavior, Addictive / Q000235:genetics* / Q000523:psychology; D050483:Dopamine Plasma Membrane Transport Proteins; D004311:Double-Blind Method; D005260:Female; D005787:Gene Frequency / Q000235:genetics; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D017448:Receptors, Dopamine D2 / Q000235:genetics*; D012907:Smoking / Q000235:genetics* / Q000523:psychology; D013315:Stress, Psychological / Q000235:genetics* / Q000523:psychology; D019914:Taq Polymerase / Q000235:genetics
D050483:Dopamine Plasma Membrane Transport Proteins; D008562:Membrane Glycoproteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D017448:Receptors, Dopamine D2; C493214:SLC6A3 protein, human; D019914:Taq Polymerase