Activation of dopamine D2 receptors decreases DARPP-32 phosphorylation in striatonigral and striatopallidal projection neurons via different mechanisms

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, Refs 1 and 13), Here we have utilized regulation of the phosphorylation of dopamine- and cyclic AMP-regulated phosphoprotein of mel. 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-2 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. (C) 1998 IBRO. Published by Elsevier Science Ltd.