Activation of dopamine D 2 receptors decreases DARPP-32 phosphorylation in striatonigral and striatopallidal projection neurons via different mechanisms

Abstract

The vast majority of striatal neurons are GABAergic medium-sized spiny neurons. These cells receive glutamatergic input from the cortex, thalamus and limbic areas and dopaminergic input from the mesencephalon. Most relevant evidence indicates that dopamine D 1 receptors are located on striatonigral projection neurons, [5, 7] and that adenosine A 2A receptors [4, 12, 14] and most dopamine D 2 receptors [5, 7, 14] are located on striatopallidal projection neurons (see, however, [1, 13]). Here we have utilized regulation of the phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein of mol. wt 32,000 (DARPP-32) to study the possible interactions among nigrostriatal dopaminergic neurons and the two classes of dopaminoceptive target neurons. We show that, in striatal slices, the D 2 receptor agonist, quinpirole, strongly inhibits the phosphorylation of DARPP-32 induced by either the D 1 receptor agonist, SKF 81297, or the A 2A receptor agonist, CGS 21680. Tetrodotoxin abolished the effect of quinpirole on the D 1 agonist-induced but not the A 2A agonist-induced phosphorylation of DARPP-32. These data indicate that: (i) adenosine A 2A and dopamine D 2 receptors interact within the same striatopallidal neurons, and (ii) D 2 receptors present on the striatopallidal neurons modulate the effects of D 1 receptors on the striatonigral neurons. Thus, a single neurotransmitter is capable of activating distinct classes of receptors on distinct populations of target neurons, which, in turn, interact with each other through intercellular communication.