A ROLE FOR CENTRAL A(3)-ADENOSINE RECEPTORS - MEDIATION OF BEHAVIORALDEPRESSANT EFFECTS

The behavioral effects of a selective A(3) adenosine receptor agonist 3-IB-MECA -6-(3-iodobenzyl)-5'-N-methylcarboxamidoadenosine) in mice a nd the localization of radioligand binding sites in mouse brain were e xamined. Low levels A(3) adenosine receptors were detected in various regions of the mouse brain (hippocampus, cortex, cerebellum, striatum) , using a radioiodinated, high-affinity A(3)-agonist radioligand [I-12 5]AB-MECA do-4-aminobenzyl)-5'-N-methylcarboxamidoadenosine) Scatchard analysis in the cerebellum showed that the K, value for binding to A( 3) receptors was 1.39 +/- 0.04 nM with a Bmax of 14.8 +/- 2.1 fmol/mg protein. 3-IB-MECA at 0.1 mg/kg i.p. was a locomotor depressant with > 50% reduction in activity. Although selective A(1) or A(2), antagonist s reversed locomotor depression elicited by selective A(1) or A(2a) ag onists, respectively, the behavioral depressant effects of 3-IB-MECA w ere unaffected. 3-IB-MECA also caused scratching in mice, which was pr evented by coadministration of the histamine antagonist cyproheptadine . The demonstration of a marked behavioral effect of A(3) receptor act ivation suggests that the A(3) receptor represents a potential new the rapeutic target.