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

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

Transcutaneous electric acupoint stimulation reduced consumption of profopol in patients undergoing laparoscopic surgery: A randomized clinical trial

“…However, HT7 and PC4 were more frequently chosen for treatment of sleep disorder and sedation. [24][25][26][27] EEG study and fMRI study have suggested the pharmacophysiology of TEAS. [28,29] Our recent study found that the sedative effect of TEAS may be due to inhibition of ascending reticular activating system.…”

Methamphetamine Activates Trace Amine Associated Receptor 1 to Regulate Astrocyte Excitatory Amino Acid Transporter-2 via Differential CREB Phosphorylation During HIV-Associated Neurocognitive Disorders

“…Non-functional mutations in mouse TAAR1 affect METH intake, hypothermia and conditioned taste aversion (82,83). Humans possess many TAAR1 variants with sensitivity to ligands (84)(85)(86)(87). However, the effects of TAAR1 variants on signaling cascades and risk for MUD, HAND, and neuropsychological disease will need to be evaluated.…”

Dopamine dysfunction in stimulant use disorders: mechanistic comparisons and implications for treatment

“…Polymorphisms in the TAAR1 gene produce functional, sub-functional and non-functional variants 104 , although the sub-functional or non-functional variants are rare. Recently, Loftis et al 105 found that a synonymous single nucleotide polymorphism (SNP) in the human TAAR1 gene was associated with increased craving in methamphetamine users. Roles for non-functional TAAR1 genotypes have been proposed in obesity 106 , schizophrenia 107 and ‘mental illness’ 108 .…”

“…Therefore, the effects of TAAR1 agonists on addictive behavior associated with both stimulant classes is hypothesized to derive from reduced striatal dopamine release. Emphasizing the importance of TAAR1 in methamphetamine addiction, a recent paper found increased craving for methamphetamine in a subset of humans with a common TAAR1 genotype 105 .…”