D2-like receptor activation does not initiate a brain docosahexaenoic acid signal in unanesthetized rats

Background: The polyunsaturated fatty acid, docosahexaenoic acid (DHA), participates in neurotransmission involving activation of calcium-independent phospholipase A(2) (iPLA(2)), which is coupled to muscarinic, cholinergic and serotonergic neuroreceptors. Drug induced activation of iPLA(2) can be measured in vivo with quantitative autoradiography using C-14-DHA as a probe. The present study used this approach to address whether a DHA signal is produced following dompaminergic (D) 2-like receptor activation with quinpirole in rat brain. Unanesthetized rats were infused intravenously with C-14-DHA one minute after saline or quinpirole infusion, and serial blood samples were collected over a 20-minute period to obtain plasma. The animals were euthanized with sodium pentobarbital and their brains excised, coronally dissected and subjected to quantitative autoradiography to derive the regional incorporation coefficient, k*, a marker of DHA signaling. Plasma labeled and unlabeled unesterified DHA concentrations were measured. Results: The incorporation coefficient (k*) for DHA did not differ significantly between quinpirole-treated and control rats in any of 81 identified brain regions. Plasma labeled DHA concentration over the 20-minute collection period (input function) and unlabeled unesterified DHA concentration did not differ significantly between the two groups. Conclusion: These findings demonstrate that D2-like receptor initiated signaling does not involve DHA as a second messenger, and likely does not involve iPLA(2) activation.