Interindividual variation in anxiety response to amphetamine: Possible role for adenosine A(2A) receptor gene variants.

Abstract

Amphetamine is thought to produce its stimulant effects mainly via the dopamine system, but its effects may also be influenced by other systems. Dopamine D1 and D2 receptors exist as heterodimers with adenosine A1 and A2A receptors, which modulate their responsiveness, suggesting that responses to amphetamine may also depend on adenosinergic function. We therefore studied the relevance of one adenosine A1 and three adenosine A2A receptor gene polymorphisms for the interindividual variability in amphetamine response in 99 healthy volunteers who received placebo or d-amphetamine (10 or 20 mg). The 1976C/T and 2592C/Tins polymorphisms of the adenosine receptor gene were associated with increases in anxiety at both doses. This is consistent with recent observations indicating a role for adenosine A2A receptor gene polymorphisms in anxiety.