Microiontophoretic studies of the effects of D‐1 and D‐2 receptor agonists on type I caudate nucleus neurons: Lack of synergistic interaction

Several lines of evidence have suggested there may be a physiologically relevant form of synergistic interaction between D‐1 and D‐2 dopamine (DA) receptors located on postsynaptic neurons in the forebrain that receive a dopaminergic innervation. Because of the theoretical importance of such an interaction with respect to understanding the normal physiology of dopaminergic systems, we evaluated effects of D‐1 and D‐2 selective, agonists, applied microiontophoretically, on the spontaneous electrical activity of a single, identifiable subpopulation of neurons within the caudate nucleus, the type I striatal neuron, in locally anesthetized, gallamine‐paralyzed rats. It was observed that the D‐2 receptor agonist quinpirole (QUIN) produced biphasic effects on cell firing rate. Low ejection currents significantly increased firing rate, while higher currents produced an inhibition. Similar effects were observed for the D‐1 agonists SKF 38393; however, the overall excitations observed at low ejection currents were far less than those observed for QUIN. When these two agonists were applied concurrently, a simple additive effect (but not synergism) was always observed. The acute reduction of striatal levels of DA, by as much as 84% (with pretreatment with α‐methyl‐p‐tyrosine, AMPT), did not alter the responsiveness of type I striatal neurons to the DA receptor agonists applied alone or in combination. These observed effects were not altered either by chloral hydrate anesthesia (in which glutamate‐driven activity was studied) or by a more severe depletion of striatal DA levels (98% depletion produced by combined pretreatment with AMPT and reserpine). © Wiley‐Liss, Inc.