Systemic administration of the adenosine A2A agonist CGS 21680 induces sedation at doses that suppress lever pressing and food intake

Adenosine A(2A) receptors are involved in the regulation of several behavioral functions. Adenosine A(2A) antagonists exert antiparkinsonian effects in animal models, and adenosine A(2A) agonists suppress locomotion and impair various aspects of motor control. The present experiments were conducted to study the effects of low doses of the adenosine A(2A) agonist CGS 21680 on lever pressing, specific parameters of food intake, and sedation. In the first experiment, the effects of CGS 21680 on fixed ratio 5 lever pressing were assessed. In the second experiment, rats were tested in 30 min feeding sessions, and also were observed for drug-induced sedation using a sedation rating scale. CGS 21680 (0.025, 0.05, 0.1 mg/kg IP) produced a dose related suppression of lever pressing, and also reduced the amount of food consumed. The feeding effect was largely dependent upon a slowing of the rate of feeding, and there was only a modest suppression of time spent feeding. Doses of CGS 21680 that suppressed lever pressing and feeding also were associated with sedation/drowsiness. In conjunction with other studies, the present results suggest that sedative effects may play an important role in some of the behavioral effects produced by systemic administration of adenosine A(2A) agonists. (c) 2008 Elsevier Inc. All rights reserved.