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

The vast majority of striatal neurons are GABAergic medium-sized spiny neur ons. These cells receive glutamatergic input from the cortex, thalamus and limbic areas and dopaminergic input from the mesencephalon. Most relevant e vidence indicates that dopamine D-1 receptors are located on striatonigral projection neurons,(5,7) and that adenosine A(2A) receptors(4,12,14) and mo st 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 o f mel. wt 32,000 (DARPP-32) to study the possible interactions among nigros triatal dopaminergic neurons and the two classes of dopaminoceptive target neurons. We show that, in striatal slices, the D-2 receptor agonist, quinpi role, strongly inhibits the phosphorylation of DARPP-32 induced by either t he D-2 receptor agonist, SKF 81297, or the A(2A) receptor agonist, CGS 2168 0. Tetrodotoxin abolished the effect of quinpirole on the D-1 agonist-induc ed but not the A(2A) agonist-induced phosphorylation of DARPP-32, These dat a indicate that: (i) adenosine A(2A) and dopamine D-2 receptors interact wi thin the same striatopallidal neurons, and (ii) D-2 receptors present on th e striatopallidal neurons modulate the effects of D-1 receptors on the stri atonigral neurons. Thus, a single neurotransmitter is capable of activating distinct classes of receptors on distinct populations of target neurons, w hich, in turn, interact with each other through intercellular communication . (C) 1998 IBRO. Published by Elsevier Science Ltd.