Home
Resources
Publications
Trace Amine-Associated Receptor Gene Polymorphism Increases Drug Craving in Individuals With Methamphetamine Dependence

Trace Amine-Associated Receptor Gene Polymorphism Increases Drug Craving in Individuals With Methamphetamine Dependence

Jennifer M Loftis, Michael Lasarev, Xiao Shi, Jodi Lapidus, Aaron Janowsky, William F Hoffman, Marilyn Huckans

PLoS One. 2019 Oct 10;14(10):e0220270.

PMID: 31600226

Abstract:

Background:
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.
Methods:
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.
Results:
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.
Conclusions:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42414931	PC4, wild type human			Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: