Discriminative-stimulus effects of adenosine analogs: mediation by adenosine A2 receptors

Squirrel monkeys were trained to discriminate either the nonselective adenosine analog 5'-N-ethylcarboxamide adenosine (NECA) or the A1-selective analog N6-cyclopentyladenosine (CPA) from saline. After i.v. injections of 0.03 mumol/kg of NECA or 1.0 mumol/kg of CPA, 10 consecutive responses on one lever produced food, whereas after i.v. injections of saline, 10 consecutive responses on the alternate lever produced food. The discriminative-stimulus effects of the adenosine analogs NECA, CPA, 2-chloroadenosine and the R- and S-isomers of N6-phenylisopropyladenosine (PIA), of the adenosine antagonists caffeine and 8-cyclopentyltheophylline (CPT), and of selected drugs from other classes (haloperidol, pentobarbital, diazepam and morphine) were determined by administering cumulative doses i.v. before sequential components of the experimental session. All adenosine analogs engendered dose-related increases in the percentage of responses on the NECA- or CPA-associated levers reaching a maximum of greater than or equal to 90%. The rank order of potency was similar in both NECA-trained and CPA-trained monkeys: NECA greater than 2-chloroadenosine greater than or equal to CPA greater than or equal to R-PIA greater than S-PIA. None of the other drugs had discriminative-stimulus effects comparable to those of the adenosine analogs. In additional studies, the nonselective adenosine antagonist caffeine or the A1-selective antagonist CPT were administered before cumulative doses of NECA or CPA. Both adenosine antagonists blocked the discriminative-stimulus effects of NECA and CPA, with CPT being about one order of magnitude more potent than caffeine.(ABSTRACT TRUNCATED AT 250 WORDS)