The differential role of A1 and A2 adenosine receptor subtypes in locomotor activity and place conditioning in rats

Previous studies have demonstrated that the non-specific adenosine antagonist caffeine possesses both motor activating and rewarding properties in a place-conditioning paradigm. The present experiments were designed to determine the relative contribution of Al and A2 adenosine receptor subtypes to these effects. The A2 adenosine antagonist CGS 15943A (0.1-10.0 mg/kg) dose-dependently produced both a place preference and enhanced locomotor activity. In contrast, the Al antagonist CPX (0.01-40.0 mg/kg) failed significantly to alter either behavioral measure. Both the Al receptor agonist CPA (0.01-10.0 mg/kg) and the A2 receptor agonist CGS 21680 (0.01-1.0 mg/kg) reliably decreased activity but failed to produce significant place conditioning. The increased;activity produced by the A2 antagonist CGS 15943A(1.0 mg/kg) was attenuated by behaviorally active doses of either CPA or CGS 21680. The place preference produced by CGS 15943A (1.0 mg/kg) was attenuated by CPA and CGS 21680, at agonist doses that failed to produce place conditioning when administered alone. In general, the results suggested that although it is the A2 receptor subtype that participates in the establishment of place conditioning and enhanced activity, both receptors participate in the diffuse depressant effects associated with adenosine.