Adenosine A2a receptors also mediate the synergistic activation of PKA by combined sub-threshold doses of several addictive drugs.102,103 Cannabinoid and opioid receptor agonists can act together or with ethanol to activate PKA at doses that would not normally activate PKA when given alone. Adenosine A2a receptor antagonists block this effect. CB1 receptor agonists acutely increase PKA-dependent DARPP-32 phosphorylation at Thr-34 in mouse dorsal striatum and NAc.88 This increase is blocked by administration of the A2a receptor antagonist KW6002.88
