Inhibition of nigrostriatal release of dopamine in the rat by adenosine receptor agonists: A 1 receptor mediation

Abstract

The stable analogues of adenosine, N-ethylcarboxamidoadenosine (NECA), R-phenylisopropyladenosine (R-PIA) and cyclohexyladenosine (CHA), dose-dependently decreased levels of 3-methoxytyramine (3-MT) in the striatum and antagonized pargyline-dependent accumulation of 3-methoxytyramine. These agents were equipotent with ED 25 values of approximately 1 mg/kg, (p.o.) in inhibiting pargyline-dependent accumulation of 3-methoxytyramine. Since CHA and R-PIA are relatively selective for A 1 receptors and NECA is almost equipotent at A 1 and A 2 sites, the data of undifferentiated potency for these 3 agents on release of dopamine (levels of 3-MT) would argue in favor of mediation of A 1 receptors in this phenomenon. This conclusion was further supported by experiments with the A 1-selective antagonist, 8-cyclopentyl-l,3-dipropylxanthine (CPDX), which antagonized the actions of CHA. Similar antagonism of CHA-dependent decreases in levels of cyclic GMP in the cerebellum, an action known to be mediated by A 1 receptors, was also observed. These data support previous studies which indicated an adenosine receptor-mediated modulation of nigrostriatal release of dopamine. In addition, the present data indicate that this is an action on A 1 receptors.