ABSTRACT
RATIONALE: Previous studies have shown that adenosine A(2A) receptors are colocalized with dopamine D(2) receptors on striatal neurons. Activation of these two receptors has antagonistic effects under a number of conditions suggesting that stimulation of adenosine A(2A) receptors may have behavioral effects resembling those produced by blockade of dopamine D(2) receptors, but this possibility has been investigated in a limited number of situations. OBJECTIVE: We compared the effects of the adenosine A(2A) agonist CGS-21680 and the preferential D(2) dopamine antagonist haloperidol in a situation in which dopamine blockade produces a distinctive pattern of behavioral effects. MATERIALS AND METHODS: Six rats were trained to lever press for food reward on a fixed ratio 15 schedule of reinforcement and then tested after being injected with various doses of CGS-21680 (0.064, 0.128, and 0.25 mg/kg) and haloperidol (0.25 and 0.1 mg/kg). RESULTS: Haloperidol produced a dose-dependent suppression of lever pressing with mean response rates declining across the duration of the test session. CGS-21680 also produced a dose-dependent suppression of responding, but this effect was not temporally graded, and responding was equivalently suppressed across the duration of the session. Additionally, CGS-21680 increased post-reinforcement pause duration to a much greater extent than did haloperidol. CONCLUSIONS: On this task, the behavioral effects of CGS-21680 do not resemble those produced by haloperidol. Several explanations of this discrepancy are possible, the most likely being that the observed behavioral effects of CGS-21680 result from an action at a site other than D(2) receptor-expressing striatal neurons.
