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

Amphetamine is thought to produce its stimulant effects mainly via the dopamine system, but its effects may also be influenced by other systems. Dopamine D 1 and D 2 receptors exist as heterodimers with adenosine A 1 and A 2A receptors, which modulate their responsiveness, suggesting that responses to amphetamine may also depend on adenosinergic function. We therefore studied the relevance of one adenosine A 1 and three adenosine A 2A 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/T ins 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 A 2A receptor gene polymorphisms in anxiety. © 2005 Wiley‐Liss, Inc.