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 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 [1-¹⁴C]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.