Adenosine agonists CGS 21680 and NECA inhibit the initiation of cocaine self-administration

Administration of the adenosine antagonist caffeine will facilitate the reinstatement of cocaine self-administration responding. This suggests that adenosine receptors may play a role in the motivational systems that regulate cocaine-seeking behaviors. If so then adenosine agonists may act to block cocaine self-administration. To test this hypothesis, the effects of the nonselective adenosine agonist NECA and of the A2A selective agonist, CGS 21680 on the self-administration of cocaine were determined. In these experiments, rats were allowed to obtain intravenous cocaine infusions (0.6 mg/kg/infusion) delivered under a Fixed Ratio 5 schedule. Treatment with either NECA or CGS 21680 in comparison to vehicle administration reduced the number of infusions received per session. This, primarily, was due to a marked increase in the latency for delivery of the first cocaine infusion. Responding after drug-induced delays tended to be at control levels. Adenosine agonists are known to have sedative effects and these actions might play a role in NECA and CGS 21680-induced increases in latencies for cocaine delivery. These results indicate that the administration of adenosine agonists may inhibit cocaine-seeking behaviors. The degree to which these actions are on motivational systems as opposed to involving less specific effects remains to be fully elucidated.