Differential effects of the adenosine A2A agonist CGS-21680 and haloperidol on food-reinforced fixed ratio responding in the rat

Abstract

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. 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. 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). 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. 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.