Effects of adenosine analogs alone and in combination with caffeine in the squirrel monkey

Effects of the adenosine analogs R-N6-phenylisopropyl-adenosine (R-PIA) and 5'-N-ethylcarboxamidoadenosine (NECA), alone and in combination with caffeine, were studied in squirrel monkeys trained to respond under multiple fixed-interval fixed-ratio schedules of reinforcement. Both drugs produced dose-related decreases in rates of responding, with little difference between effects in the two components. NECA was about ten times more potent than R-PIA in producing these effects, the order of potency suggests that these effects may be mediated by actions at A2-adenosine receptors. Effects of either drug were antagonized by caffeine. Caffeine when administered alone increased rates of responding. The increases in response rates produced by caffeine were altered by R-PIA only at doses of R-PIA that alone decreased response rates. Effects of caffeine were either enhanced or attenuated by doses of NECA that were inactive when administered alone. These results do not support the notion that increases in rates of behavior, e.g., psychomotor-stimulant effects, produced by caffeine are due to its antagonist actions at adenosine receptors.