Discriminative stimulus properties of L-phenylisopropyl adenosine: blockade by caffeine and generalization to 2-chloroadenosine.
Recent neurochemical data on the effects of activation and blockade of adenosine A1 receptors has suggested a direct role of adenosine in neurotransmission. The present research used a drug discrimination procedure to test the hypotheses that A1 adenosine receptor activation could serve as a discriminative stimulus and that caffeine, a drug believed to be an A1 receptor antagonist, could block the adenosine discrimination. Food-deprived rats were trained to press one of two levers on an FR 10 schedule of food-pellet delivery. Responses on one lever were reinforced following i.p. injection of N6 - (L-phenylisopropyl) adenosine (L-PIA); responses on the other lever were reinforced following i.p. injection of saline. L-PIA training dose was increased from 0.064 to 0.08 mg/kg L-PIA in the course of the study. Subjects required an average of 91 sessions to acquire this discrimination. Stimulus control by L-PIA was dose-dependent, with the ED-50 being approximately 0.03 mg/kg. 2-Chloroadenosine (2CA) generalized to L-PIA with a tenth the potency. Caffeine blocked L-PIA-induced lever selection. These results indicate that 1) rats can be trained to discriminate L-PIA from saline in a two-lever food-reinforced task and 2) the discriminative stimuli produced by L-PIA are based on its agonistic action at the adenosine A1 receptor.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D004192:Discrimination, Psychological / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005793:Generalization, Psychological / Q000187:drug effects*; D008297:Male; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D015762:2-Chloroadenosine; D010660:Phenylisopropyladenosine; D002110:Caffeine; D000241:Adenosine