title: Interactions in the behavioral effects of methylxanthines and adenosine derivatives.
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 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.
mesh_terms: 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*
chemical_list: D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014970:Xanthines; D010660:Phenylisopropyladenosine; D002110:Caffeine; D000241:Adenosine; D003975:Diazepam