Antagonism of the behavioral effects of L-phenylisopropyladenosine (L-PIA) by caffeine and its metabolites.

Three male Sprague-Dawley strain rats were trained to respond under a multi-component time out 5 min variable ratio 15 (VR15) schedule of food reinforcement. Cumulative, within session dose-effect curves were determined for L-PIA alone and after methylxanthine pretreatment. L-PIA alone produced dose related decreases on VR15 responding at doses between 0.032 and 0.178 mg/kg. Significant antagonism of L-PIA was demonstrated from pretreatment with caffeine, theophylline, theobromine, paraxanthine, 3-methylxanthine, and 7-methylxanthine. No antagonism of L-PIA was observed following pretreatment with 1-methylxanthine. Consistent with the adenosine receptor blockade hypothesis, caffeine also antagonized the effects of 5'-N-ethylcarboxamide adenosine (NECA) on VR15 responding.