Effects of selected analogs of adenosine on schedule-controlled behavior in rats.

Acute administration of N6(L-phenylisopropyl)adenosine (L-PIA; 0.01-0.178 mg/kg, s.c.), N6-cyclohexyladenosine (CHA; 0.01-0.178 mg/kg, s.c.), 2-chloroadenosine (2-CA; 0.32-0.56 mg/kg, s.c.), N6-cycloheptyladenosine (CHPA; 0.032-1.0 mg/kg, s.c.), N6-phenyladenosine (PA; 0.1-1.0 mg/kg, s.c.), N6(D-phenylisopropyl)adenosine (D-PIA; 0.32-1.0 mg/kg, s.c.) and N6-benzyladenosine (BA; 1.0-17.8 mg/kg, s.c.) produced dose-related decreases in responding under a fixed-ratio (FR) schedule of food reinforcement. Dose-effect curves were determined by administering cumulative doses (s.c.) during periods that preceded the sequential components of the schedule. Neither 2-chloroadenine arabinoside (2-CAB) nor 2',5'-dideoxyadenosine (2',5'-DDA) altered fixed-ratio responding at the doses studied (0.1-3.2 and 1.0 and 3.2, respectively). Caffeine (0.32 and 3.2 mg/kg) antagonized the behavioral effects of L-PIA in a dose-related, surmountable manner. Daily administration of L-PIA (0.1 mg/kg) resulted in the development of tolerance to the effects of L-PIA decreasing rate and cross-tolerance to other analogs of adenosine (CHA, BA, D-PIA). No cross-tolerance was produced to caffeine, levorphanol or chlordiazepoxide. The activity and order of potency of the analogs of adenosine tested were consistent with the effects of agonists at A1 adenosine receptors. Furthermore, the results demonstrate that the behavioral effects of N6- and 2-chlorine-substituted analogs of adenosine probably act through similar CNS mechanism(s).