Dopaminergic modulation of glutamate-induced excitations of neurons in the neostriatum and nucleus accumbens of awake, unrestrained rats.

1. Single-unit recording and iontophoresis were used in awake, unrestrained rats to assess the action of dopamine (DA) and glutamate (GLU) on the spontaneous activity of neurons in the neostriatum and nucleus accumbens. 2. A total of 88 neurons (40 neostriatal and 48 accumbal) was recorded from 7 rats during 13 recording sessions. During quiet rest, spontaneously active neurons discharged at a slow rate and irregular pattern of activity. Accumbal neurons had a significantly faster level of basal activity than neostriatal neurons (modal values of 10.3 vs. 2.1 imp/s, respectively). 3. Neuronal responses to separate applications of DA and GLU (5-80 nA; 15-30 s) were tested on 40 and 76 units (195 and 227 applications), respectively, during the quiet resting period. The effect of prolonged DA iontophoresis (5-80 nA; 2-3 min) on GLU-induced changes in impulse activity was tested on 38 units (72 applications). 4. GLU activated all cells in both structures. This response appeared with a latency of 0.5-4.0 s at different ejection currents (5-40 nA; mean threshold of 22.2 nA) and was highly variable (103-11,520% of basal activity). Response magnitude correlated strongly with the rate of basal activity (r = 0.822). 5. DA inhibited 75% of spontaneously active neostriatal and accumbal cells with a mean threshold of 20.4 nA. In contrast to the GLU excitation, the DA-induced inhibition was relatively weak in magnitude (10-90% of basal activity) and occurred with relatively longer on- and offset latencies than GLU (2-20 s). The inhibitory effect of DA was absent during phasic activations of neuronal activity associated with movement. Two neostriatal neurons responded to DA with a dose-dependent excitation. 6. Prolonged DA iontophoresis altered both basal impulse activity (causing a decrease in 36 of 72 applications and an increase in 4) and the magnitude of the GLU-induced activation (decreasing it in 27 of 72 applications and increasing it in 12). The net result was an overall enhancement of the GLU response relative to the DA-induced change in basal activity (74% of cases). This increase in the GLU response occurred at relatively low DA ejection currents (10-30 nA). It was stronger in the nucleus accumbens than in the neostriatum and was most evident on cells having both a moderate level of basal activity and a relatively small initial response to GLU. When DA was ejected at high currents (> 40 nA) and/or the magnitude of the preceding GLU-induced activation was high (> 800% of basal activity), DA tended to decrease the GLU response. 7. DA appears to exert a slight depression of striatal and accumbal activity, which has the effect of amplifying the phasic activation induced by GLU. Because forebrain DA release occurs in response to behaviorally important stimuli, the DA-induced modulation of the GLU response may play an important role in regulating goal-directed behavior.