Opposite responses in the striato-nigral substance P system to D1 and D2 receptor activation.

The roles of different dopamine receptors in mediating the responses of the striato-nigral substance P (SP) feedback loop were investigated. Subacute treatment of rats with the D1 agonist, SK&F 38393, produced a significant decrease in SP content in the substantia nigra whereas treatment with the D2 agonist, RU 24926, elevated nigral SP concentrations. Consequently, the elevation in nigral SP content which occurs following treatment with methamphetamine is likely a D2-mediated event. This conclusion is supported by our observation that the D2 antagonist, sulpiride, totally blocked the methamphetamine effect. These findings suggest that D1 and D2 receptors mediate opposing influences on the SP feedback system.