Interactions in the behavioral effects of methylxanthines and adenosine derivatives.
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 mumol/kg and higher depressed locomotor activity, lower doses (0.01 and 0.05 mumol/kg) augmented locomotor activity. At the doses evaluated, caffeine did not further augment the L-PIA (0.05 mumol/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 two agents. At behaviorally effective doses, L-PIA did not alter blood pressure or heart rate, but elicited some premature ventricular contractions which, however, occurred to a similar extent at locomotor depressant and stimulant doses of L-PIA. Brain levels of L-PIA at the lowest behaviorally active doses were adequate to occupy more than 50% of adenosine receptors. Thus, the behavioral effects of L-PIA appeared to be mediated in the brain and were not secondary to the cardiovascular effects.
D000241:Adenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology; D005117:Cardiac Complexes, Premature / Q000139:chemically induced; D003975:Diazepam / Q000494:pharmacology*; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009043:Motor Activity / Q000187:drug effects*; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects; D011983:Receptors, Purinergic; D013268:Stimulation, Chemical; D014970:Xanthines / Q000494:pharmacology*
D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014970:Xanthines; D010660:Phenylisopropyladenosine; D002110:Caffeine; D000241:Adenosine; D003975:Diazepam