Imaging apomorphine stimulation of brain arachidonic acid signaling via D2-like receptors in unanesthetized rats

Rationale and objective Because of the important role of dopamine in neurotransmission, it would be useful to be able to image brain dopamine receptor-mediated signal transduction in animals and humans. Administering the D-1-D-2 receptor agonist apomorphine may allow us to do this, as the D-2-like receptor is reported to be coupled to cytosolic phospholipase A(2) activation and arachidonic acid (AA) release from membrane phospholipid. Methods Unanesthetized adult rats were given intraperitoneally apomorphine (0.5 mg/kg) or saline, with or without pretreatment with 6 mg/kg intravenous raclopride, a D-2/D-3 receptor antagonist. [1-C-14]AA was injected intravenously, then AA incorporation coefficients k*-brain radioactivity divided by integrated plasma radioactivity-markers of AA signaling, were measured using quantitative autoradiography in 62 brain regions. Results Apomorphine significantly elevated k* in 26 brain regions, including the frontal cortex, motor and somatosensory cortex, caudate-putamen, thalamic nuclei, and nucleus accumbens. Raclopride alone did not change baseline values of k*, but raclopride pretreatment prevented the apomorphine-induced increments in k*. Conclusions A mixed D-1-D-2 receptor agonist, apomorphine, increased the AA signal by activating only D-2-like receptors in brain circuits containing regions with high D-2-like receptor densities. Thus, apomorphine might be used with positron emission tomography to image brain D-2-like receptor-mediated AA signaling in humans in health and disease.