INTERACTIONS IN THE BEHAVIORAL-EFFECTS OF METHYLXANTHINES AND ADENOSINE DERIVATIVES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 227  (1) , 167-173
Abstract
The role of adenosine receptors in behavioral effects of alkylxanthines was evaluated in mice. The relative potencies of alkylxanthines in reversing locomotor activity depression elicited by L-phenylisopropyladenosine (L-PIA) were similar to relative potencies in competing for adenosine receptors labeled by [3H]cyclohexyladenosine. Whereas L-PIA at i.p. doses of 0.10 .mu.mol/kg and higher depressed locomotor activity, lower doses (0.01 and 0.05 .mu.mol/kg) augmented locomotor activity. At the doses evaluated, caffeine did not further augment the L-PIA (0.05 .mu.mol/kg)-enhanced locomotor activity. Low doses of diazepam, like L-PIA, augmented locomotor activity. Combining locomotor depressant doses of diazepam and caffeine produced a paradoxical stimulation of activity, as observed also for L-PIA and caffeine. Low doses of diazepam but not L-PIA increased crossings between the light and dark sites in a shuttle box, indicating a difference in the behavioral profile of these 2 agents. At behaviorally effective doses, L-PIA did not alter blood pressure or heart rate, but elicited some premature ventricular contractions which occurred to a similar extent at locomotor depressant and stimulant doses. Brain levels of L-PIA at the lowest behaviorally active doses were adequate to occupy more than 50% of adenosine receptors. The behavioral effects of L-PIA appeared to be mediated in the brain and were not secondary to the cardiovascular effects.