Trace amine-associated receptor gene polymorphism increases drug craving in individuals with methamphetamine dependence

Autoři: Jennifer M. Loftis aff001;  Michael Lasarev aff003;  Xiao Shi aff001;  Jodi Lapidus aff003;  Aaron Janowsky aff001;  William F. Hoffman aff001;  Marilyn Huckans aff001
Působiště autorů: Research & Development Service, VA Portland Health Care System, Portland, OR, United States of America aff001;  Department of Psychiatry, Oregon Health & Science University, Portland, OR, United States of America aff002;  Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland, OR, United States of America aff003;  Oregon Health & Science University and Portland State University School of Public Health, Portland, OR, United States of America aff004;  Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR, United States of America aff005;  Mental Health and Clinical Neurosciences Division, VA Portland Health Care System, Portland, OR, United States of America aff006
Vyšlo v časopise: PLoS ONE 14(10)
Kategorie: Research Article



Methamphetamine (MA) is a potent agonist at the trace amine-associated receptor 1 (TAAR1). This study evaluated a common variant (CV) in the human TAAR1 gene, synonymous single nucleotide polymorphism (SNP) V288V, to determine the involvement of TAAR1 in MA dependence.


Participants (n = 106) with active MA dependence (MA-ACT), in remission from MA dependence (MA-REM), with active polysubstance dependence, in remission from polysubstance dependence, and with no history of substance dependence completed neuropsychiatric symptom questionnaires and provided blood samples. In vitro expression and function of CV and wild type TAAR1 receptors were also measured.


The V288V polymorphism demonstrated a 40% increase in TAAR1 protein expression in cell culture, but message sequence and protein function were unchanged, suggesting an increase in translation efficiency. Principal components analysis resolved neuropsychiatric symptoms into four components, PC1 (depression, anxiety, memory, and fatigue), PC2 (pain), PC3 (drug and alcohol craving), and PC4 (sleep disturbances). Analyses of study group and TAAR1 genotype revealed a significant interaction for PC3 (craving response) (p = 0.003). The control group showed no difference in PC3 associated with TAAR1, while adjusted mean craving for the MA-ACT and MA-REM groups, among those with at least one copy of V288V, was estimated to be, respectively, 1.55 (p = 0.036) and 1.77 (p = 0.071) times the adjusted mean craving for those without the TAAR1 SNP.


Neuroadaptation to chronic MA use may be altered by TAAR1 genotype and result in increased dopamine signaling and craving in individuals with the V288V genotype.

Klíčová slova:

Addiction – Alcohol consumption – Alcoholism – Caffeine – Molecular genetics – Neuropsychological testing – Sleep – Drug addiction


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