Abstract
Several lines of evidence suggest that the dopaminergic nervous system contributes to methamphetamine (METH) dependence, and there is increasing evidence of antagonistic interactions between dopamine and adenosine receptors in METH abusers. We therefore hypothesized that variations in the A1 adenosine receptor (ADORA1) gene modify genetic susceptibility to METH dependence/psychosis. In this study, we identified 7 single nucleotide polymorphisms (SNPs) in exons and exon-intron boundaries of the ADORA1 gene in a Japanese population. A total of 171 patients and 229 controls were used for an association analysis between these SNPs and METH dependence/psychosis. No significant differences were observed in either the genotypic or allelic frequencies between METH dependent/psychotic patients and controls. A global test of differentiation among samples based on haplotype frequencies showed no significant association. In the clinical feature analyses, no significant associations were observed among latency of psychosis, prognosis of psychosis, and spontaneous relapse. These results suggest that the ADORA1 gene variants may make little or no contribution to vulnerability to METH dependence/psychosis.
Highlights
Methamphetamine (METH) is a psychomotor stimulant with high liability for abuse, and METH abuse has become a very serious social problem in Japan [1]
Dopamine D1 and D2 receptors form heterodimeric complexes with adenosine A1 and A2a receptors respectly, which modulate their responsiveness [6,7,8,9], suggesting that responses to amphetamines may depend on adenosinergic function
1570-159X/11 $58.00+.00 agonists protect against METH-induced neurotoxicity, and amphetamine-induced stereotypy and locomotor activity, and reduce the acquisition of conditioned place preference induced by amphetamine [12,13,14,15]. These results suggest that adenosine A1 receptors play important roles in the expression of METH-induced neurotoxicities and behaviors
Summary
Methamphetamine (METH) is a psychomotor stimulant with high liability for abuse, and METH abuse has become a very serious social problem in Japan [1]. Chronic METH abusers have been shown to have persistent dopaminergic deficits [2, 3]. Amphetamines are thought to produce their stimulant effects mainly via the dopaminergic system [4, 5], other systems may be involved. Dopamine D1 and D2 receptors form heterodimeric complexes with adenosine A1 and A2a receptors respectly, which modulate their responsiveness [6,7,8,9], suggesting that responses to amphetamines may depend on adenosinergic function. Several lines of evidence suggest that adenosine A1 receptors play a role in inhibiting the effects of METH. Adenosine receptor antagonists potentiate the effects of lower METH doses and substitute for the discriminative stimulus effects of METH [10, 11].
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