Vol. 300, Issue 3, 850-861, March 2002

Effects of Individual and Concurrent Stimulation of Striatal D₁ and D₂ Dopamine Receptors on Electrophysiological and Behavioral Output from Rat Basal Ganglia

Barbara L. Waszczak, Lynn P. Martin, Heather E. Finlay, Natalie Zahr and James R. Stellar

Departments of Pharmaceutical Sciences and Psychology, Northeastern University, Boston, Massachusetts

Bilateral infusions of d-amphetamine into the rat ventral-lateral striatum (VLS) were previously shown to cause a robust behavioral activation that was correlated temporally with a net increase in firing of substantia nigra pars reticulata (SNpr) neurons, a response opposite predictions of the basal ganglia model. The current studies assessed the individual and cooperative contributions of striatal D₁ and D₂ dopamine receptors to these responses. Bilateral infusions into VLS of the D₁/D₂ agonist apomorphine (10 µg/µl/side) caused intense oral movements and sniffing, and an overall increase in SNpr cell firing to 133% of basal rates, similar to effects of d-amphetamine. However, when striatal D₂ receptors were stimulated selectively by infusions of quinpirole (30 µg/µl/side) + the D₁ antagonist R-(+)-7-chloro-8-hydroxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine (SCH 23390; 10 µg/µl/side), no behavioral response and only modest and variable changes in SNpr cell firing were observed. Selective stimulation of striatal D₁ receptors by (±) 6-chloro-APB hydrobromide (SKF 82958; 10 µg/µl/side) + the D₂ antagonist cis-N-(1-benzyl-2-methyl-pyrrolidin-3-yl)-5-chloro-2-methoxy-4-methyl-aminobenzamide (YM 09151-2; 2 µg/µl/side) caused a weak but sustained increase in oral movements and modestly increased SNpr cell firing, but neither response was of the magnitude observed with apomorphine. When the two agonists were infused concurrently, however, robust oral movements and sniffing again occurred over the same time period that a majority of SNpr cells exhibited marked, sometimes extreme and fluctuating, changes in firing (net increase, 117% of basal rates). These data confirm that concurrent striatal D₁/D₂ receptor stimulation elicits a strong motor activation that is correlated temporally with a net excitation rather than inhibition of SNpr firing, and reveal that D₁ and D₂ receptors interact synergistically within the striatum to stimulate both forms of output.