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Published on: November 21, 2012
OPRM1 gene variants modulate amphetamine-induced euphoria in humans
A M Dlugos1, A Hamidovic, C Hodgkinson
1Department of Psychiatry, University of Münster, Münster, Germany.
Genes, Brain, and Behavior
|October 30, 2010
Summary
Genetic variations in the micro-opioid receptor influence how people experience amphetamine. Specific gene variants and haplotypes are linked to increased feelings of euphoria and stimulation from amphetamine use.
Area of Science:
- Neuroscience
- Pharmacogenetics
- Genetics
Background:
- The micro-opioid receptor (OPRM1) plays a crucial role in the rewarding effects of opioids and psychostimulants.
- Understanding the genetic basis of individual responses to amphetamine is essential for addressing psychostimulant abuse.
Purpose of the Study:
- To investigate the association between subjective responses to amphetamine and genetic polymorphisms and haplotypes in the OPRM1 gene.
- To explore how variations in OPRM1 influence self-reported euphoria, energy, and stimulation after amphetamine administration.
Main Methods:
- 162 Caucasian volunteers received placebo or d-amphetamine (10 and 20 mg) across three sessions.
- Subjective effects were measured using the Addiction Research Center Inventory 49-item questionnaire (ARCI-49).
- Associations between OPRM1 genetic variants (SNPs and haplotypes) and ARCI-49 scores were analyzed.
Main Results:
- Intronic SNPs rs510769 and rs2281617 in OPRM1 were significantly associated with higher Euphoria, Energy, and Stimulation ratings after 10 mg amphetamine.
- A two-SNP haplotype (rs1799971 and rs510769) and a three-SNP haplotype (rs1918760, rs2281617, and rs1998220) were also linked to enhanced subjective amphetamine effects.
Conclusions:
- Genetic variability in the OPRM1 gene significantly influences the subjective effects of amphetamine.
- These findings suggest potential genetic targets for novel prevention and treatment strategies for psychostimulant abuse.
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