D2 but not D1 dopamine receptor stimulation augments brain signaling involving arachidonic acid in unanesthetized rats

Rationale and objectives: Signal transduction involving the activation of phospholipase A(2) (PLA(2)) to release arachidonic acid (AA) from membrane phospholipids, when coupled to dopamine D-1- and D-2-type receptors, can be imaged in rats having a chronic unilateral lesion of the substantia nigra. It is not known, however, if the signaling responses occur in the absence of a lesion. To determine this, we used our in vivo fatty acid method to measure signaling in response to D-1 and D-2 receptor a nists given acutely to unanesthetized rats. Methods: [1-C-14] AA was injected intravenously in unanesthetized rats, and incorporation coefficients k* for AA (brain radioactivity/integrated plasma radioactivity) were measured using quantitative autoradiography in 61 brain regions. The animals were administered i.v. the D-2 receptor agonist, quinpirole (1 mg kg(-1), i.v.), the D-1 receptor agonist SKF-38393 (5 mg kg(-1), i.v.), or vehicle/saline. Results: Quinpirole increased k* significantly in multiple brain regions rich in D-2-type receptors, whereas SKF-38393 did not change k* significantly in any of the 61 regions examined. Conclusions: In the intact rat brain, D-2 but not D-1 receptors are coupled to the activation of PLA(2) and the release of AA.