Stereoselective behavioral effects of N6-phenylisopropyl-adenosine and antagonism by caffeine.
Effects of the (-)- and (+)-isomers of N6-(phenylisopropyl)-adenosine (PIA) were studied in rats trained to respond under fixed-interval and fixed-ratio schedules of food reinforcement. Both isomers of PIA decreased response rates; however, the (-)-isomer decreased response rates at doses as low as 0.1 microM/kg and was 100-300 times more potent than the (+)-isomer. The potency differences suggest that the effects observed were due to actions at A1-adenosine receptors. Caffeine, an adenosine-receptor antagonist, when administered alone in doses of 10-154 microM/kg, increased response rates under the fixed-interval schedule and did not affect rates of responding under the fixed-ratio schedule. Higher doses decreased response rates under both schedules. Caffeine shifted the (-)-PIA dose-effect curve to the right. At a low dose of caffeine (25.7 microM/kg), which alone modestly increased response rates under the 5-min fixed-interval schedule, the disruptions in rates and patterns of responding produced by (-)-PIA were restored to resemble control performances. The higher dose of caffeine (77.2 microM/kg), which alone produced larger increases in rates of responding under the fixed-interval schedule, restored overall response rates to control levels when administered in combination with (-)-PIA. However, patterns of responding after the combination of doses remained disrupted. These effects suggest that some of the behavioral effects of caffeine are a result of mechanisms other than adenosine-receptor blockade.
D000241:Adenosine / Q000031:analogs & derivatives*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D003116:Color; D003216:Conditioning, Operant / Q000187:drug effects*; D005502:Food; D008297:Male; D010660:Phenylisopropyladenosine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D012055:Reinforcement Schedule; D013237:Stereoisomerism
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D010660:Phenylisopropyladenosine; D002110:Caffeine; D000241:Adenosine