EXCITATION OF TYPE-II ANTERIOR CAUDATE NEURONS BY STIMULATION OF DOPAMINE D-3 RECEPTORS

Previous studies have demonstrated that both direct- and indirect-acti ng dopamine (DA) receptor agonists excite type II neurons in the anter ior caudate (CN) by stimulation of DA receptors belonging to the D2 re ceptor subfamily (D-2, D-3, D-4 receptor subtypes). In the present stu dy, pramipexole, a D-3-preferring DA agonist effective in treating Par kinson's disease, excited type II anterior CN neurons. As with other d irect-acting agonists, excitation of the CN neurons occurred only at d oses above those that silenced DA neurons in the substantia nigra pars compacta (SNPC). Although more potent than pramipexole in inhibiting SNPC cells, PNU-91356A, a D-2-preferring agonist, did not excite type II CN cells. The D-3-preferring antagonist (+)-AJ76 was weaker than ha loperidol, a D-2-preferring antagonist, in reversing the effects of am phetamine on firing rates in dopaminergic neurons in both the SNPC and the CN. However, in relationship to its potency in the SNPC, (+)-AJ76 was more potent than haloperidol in the CN. PNU-101387, a selective D -4 antagonist, did not alter amphetamine-induced stimulation of type I I CN neurons. We conclude that DA agonists may excite type II anterior CN neurons via D-3 receptor activation. The stimulation of these neur ons may contribute to the anti-parkinsonian effects of pramipexole. (C ) 1997 Elsevier Science B.V.