Dopamine receptor-mediated mechanisms involved in the expression of learned activity of primate striatal neurons

To understand the mechanisms by which basal ganglia neurons express acquired activities during and after behavioral learning, selective dopamine (DA) receptor antagonists were applied while recording the activity of striatal neurons in monkeys performing behavioral tasks. In experiment 1, a monkey was trained to associate a click sound with a drop of reward water. DA receptor antagonists were administered by micropressure using a stainless steel injection cannula (300 microm ID) through which a Teflon-coated tungsten wire for recording neuronal activity had been threaded. Responses to sound by tonically active neurons (TANs), a class of neurons in the primate striatum, were recorded through a tungsten wire electrode during the application of either D1- or D2-class DA receptor antagonists (total volume <1 microl, at a rate of 1 microl/5-10 min). Application of the D2-class antagonist, (-)-sulpiride (20 micrograms/microl, 58 mM, pH 6.8), abolished the responses of four of five TANs examined. In another five TANs, neither the D2-class antagonist nor the D1-class antagonists, SCH23390 (10 micrograms/microl, 31 mM, pH 5.7) or cis-flupenthixol (30 micrograms/microl, 59 mM, pH 6.6) significantly suppressed responses. In experiment 2, four- or five-barreled glass microelectrodes were inserted into the striatum. The central barrel was used for extracellular recording of activity of TANs. Each DA receptor antagonist was iontophoretically applied through one of the surrounding barrels. SCH23390 (10 mM, pH 4.5) and (-)-sulpiride (10 mM, pH 4.5) were used. The effects of iontophoresis of both D1- and D2-class antagonists were examined in 40 TANs. Of 40 TANs from which recordings were made, responses were suppressed exclusively by the D2-class antagonist in 19 TANs, exclusively by the D1-class antagonist in 3 TANs, and by both D1- and D2-class antagonists in 7 TANs. When 0.9% NaCl, saline, was applied by pressure (<1 microl) or by iontophoresis (<30 nA) as a control, neither the background discharge rates nor the responses of TANs were significantly influenced. Background discharge rate of TANs was also not affected by D1- or D2-class antagonists applied by either micropressure injection or iontophoresis. It was concluded that the nigrostriatal DA system enables TANs to express learned activity primarily through D2-class and partly through D1-class receptor-mediated mechanisms in the striatum.