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

Abstract

Rationale and objectives: Signal transduction involving the activation of phospholipase A2 (PLA2) to release arachidonic acid (AA) from membrane phospholipids, when coupled to dopamine D1- and D2-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 D1 and D2 receptor agonists given acutely to unanesthetized rats.

Methods: [1-(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 D2 receptor agonist, quinpirole (1 mg kg(-1), i.v.), the D1 receptor agonist SKF-38393 (5 mg kg(-1), i.v.), or vehicle/saline.

Results: Quinpirole increased k* significantly in multiple brain regions rich in D2-type receptors, whereas SKF-38393 did not change k* significantly in any of the 61 regions examined.

Conclusions: In the intact rat brain, D2 but not D1 receptors are coupled to the activation of PLA2 and the release of AA.