Stereoselective behavioral effects of N6-phenylisopropyl-adenosine and antagonism by caffeine

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Abstract
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 μM/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 μM/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 μM/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 μM/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.