D sub(2) but not D sub(1) dopamine receptor stimulation augments brain signaling involving arachidonic acid in unanesthetized rats

Rationale and objectives: Signal transduction involving the activation of phospholipase A sub(2) (PLA sub(2)) to release arachidonic acid (AA) from membrane phospholipids, when coupled to dopamine D sub(1)- and D sub(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 sub(1) and D sub(2) receptor agonists given acutely to unanesthetized rats. Methods: [1- super(14)C]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 sub(2) receptor agonist, quinpirole (1 mg kg super(-1), i.v.), the D sub(1) receptor agonist SKF-38393 (5 mg kg super(-1), i.v.), or vehicle/saline. Results: Quinpirole increased k* significantly in multiple brain regions rich in D sub(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 sub(2) but not D sub(1) receptors are coupled to the activation of PLA sub(2) and the release of AA.