ADENOSINE-A(2A) RECEPTORS IN THE NUCLEUS-ACCUMBENS MEDIATE LOCOMOTOR DEPRESSION (VOL 31, PG 397, 1993)

The effects on locomotor activity (LA) of selective agonists for adeno sine receptor subtypes were examined in mice following bilateral injec tions into the nucleus accumbens (ACB). The ACB is not only richly inn ervated by dopaminergic (DA) terminals but also exhibits the highest d ensities of adenosine A2a receptors in the brain. CGS 21680 l)phenethy lamino]-5'-N-ethylcarboxamidoadenosine), a potent and highly selective adenosine A2a receptor agonist, elicited pronounced, dose-related red uctions in LA (ID50 dosage = 0.0031 nmol/mouse). NECA (5'-N-ethylcarbo xamidoadenosine), a mixed adenosine receptor agonist which exhibits hi gh selectivity and potency at striatal A2a receptors, similarly elicit ed dose-related reductions in LA (ID50 dosage = 0.0023 nmol/mouse). In contrast, intra-ACB injections of CPA (N6-cyclopentyladenosine), a hi ghly selective agonist for adenosine A1 receptors, did not exert any s ignificant effects on LA, even at 2.0 nmol/mouse, a dosage at which bo th CGS 21680 and NECA depressed LA by almost 90% compared to vehicle c ontrols. Further, the pronounced locomoter depression elicited by intr a-ACB injections of both CGS 21680 and NECA, at approximately the ID65 dosage, was significantly antagonized by IP pretreatment with DMPX. ( 3,7-dimethyl-1-proparglyxanthine), an adenosine receptor antagonist wi th selectivity for A2 receptors in the striatum, at a dosage (0.15 mum ol/mouse) which alone had no significant effect on LA. These observati ons provide support for the notion that adenosine may selectively modu late DA-mediated mesolimbic behavioral circuits via agonist actions at a population of A2a receptors densely concentrated in the ventral str iatum.