Psychomotor stimulant effects of caffeine alone and in combination with an adenosine analog in the squirrel monkey

Responding of squirrel monkeys was maintained under a fixed-interval schedule of food presentation in one group of subjects or electric-shock presentation in a second group. Rates of responding were decreased in a dose-dependent manner by the (-)-isomer of 6N-[1-methyl-2-phenylethyl]-adenosine (PIA) under both schedules. Caffeine shifted the (-)-PIA dose-effect curve to the right in a dose-dependent manner. Single administrations of 15.0 mg/kg of caffeine had (-)-PIA-antagonist effects for up to 48 hr. Caffeine administered alone increased rates of responding at intermediate doses, and decreased rates at the highest doses. The increases in response rates produced by intermediate doses of caffeine were appreciably diminished at 24 hr. Doses of (-)-PIA that were inactive when administered alone had little effect on the increases in response rate produced by caffeine. Doses of (-)-PIA that decreased response rates when administered alone attenuated the increase in response rates produced by caffeine. Increases in response rates produced by (+)-amphetamine were altered by (-)-PIA similarly to the manner in which (-)-PIA altered the effects of caffeine. Increases in response rates produced by caffeine were altered by chlorpromazine similarly to the manner in which (-)-PIA altered effects of caffeine. When caffeine was administered daily, as one 15.0-mg/kg injection after experimental sessions, tolerance developed to the response rate increasing effects of caffeine.(ABSTRACT TRUNCATED AT 250 WORDS)