Haloperidol downregulates phospholipase A(2) signaling in rat basal ganglia circuits

Our laboratory has developed an in vivo method to quantitatively evaluate p hospholipase A(2) (PLA(2))-mediated signal transduction in brain regions of rodents. In this method, quantitative autoradiography is used to identify brain uptake of intravenously injected, radiolabeled arachidonic acid ([H-3 ]AA). Dopamine D-2 receptors are coupled to G-proteins that activate PLA(2) , releasing AA from the stereospecifically numbered (sn) 2 position of phos pholipids, and regional [H-3]AA uptake is proportional to the rate of relea se. In the present experiment, the D, antagonist haloperidol (1.0 mg/kg i.p .) or the drug vehicle was administered to male adult rats for 21 days. Rat s were infused 3 days later with 1.75 mCi/kg [H-3]AA (i.v.), anesthetized a nd decapitated 20 min after infusion onset, and brains were processed for q uantitative autoradiography. Chronic haloperidol significantly decreased [H -3]AA incorporation in two primary dopaminergic basal ganglia-frontal corte x circuits, the mesocorticolimbic and nigrostriatal systems, while insignif icant changes in AA incorporation were noted in other brain regions. These results suggest that one mechanism by which haloperidol exerts its effect i s by downregulating D-2-mediated PLA(2) signaling involving AA release in b asal ganglia-frontal cortex circuitry. Published by Elsevier Science B.V.