D-Amphetamine stimulates D(2) dopamine receptor-mediated brain signaling involving arachidonic acid in unanesthetized rats.
In rat brain, dopaminergic D(2)-like but not D(1)-like receptors can be coupled to phospholipase A(2) (PLA(2)) activation, to release the second messenger, arachidonic acid (AA, 20:4n-6), from membrane phospholipids. In this study, we hypothesized that D-amphetamine, a dopamine-releasing agent, could initiate such AA signaling. The incorporation coefficient, k* (brain radioactivity/integrated plasma radioactivity) for AA, a marker of the signal, was determined in 62 brain regions of unanesthetized rats that were administered i.p. saline, D-amphetamine (2.5 or 0.5 mg/kg i.p.), or the D(2)-like receptor antagonist raclopride (6 mg/kg, i.v.) before saline or 2.5 mg/kg D-amphetamine. After injecting [1-(14)C]AA intravenously, k* was measured by quantitative autoradiography. Compared to saline-treated controls, D-amphetamine 2.5 mg/kg i.p. increased k* significantly in 27 brain areas rich in D(2)-like receptors. Significant increases were evident in neocortical, extrapyramidal, and limbic regions. Pretreatment with raclopride blocked the increments, but raclopride alone did not alter baseline values of k*. In independent experiments, D-amphetamine 0.5 mg/kg i.p. increased k* significantly in only seven regions, including the nucleus accumbens and layer IV neocortical regions. These results indicate that D-amphetamine can indirectly activate brain PLA(2) in the unanesthetized rat, and that activation is initiated entirely at D(2)-like receptors. D-Amphetamine's low-dose effects are consistent with other evidence that the nucleus accumbens, considered a reward center, is particularly sensitive to the drug.Journal of Cerebral Blood Flow & Metabolism (2006) 26, 1378-1388. doi:10.1038/sj.jcbfm.9600290; published online 1 March 2006.[1]References
- D-Amphetamine stimulates D(2) dopamine receptor-mediated brain signaling involving arachidonic acid in unanesthetized rats. Bhattacharjee, A.K., Chang, L., White, L., Bazinet, R.P., Rapoport, S.I. J. Cereb. Blood Flow Metab. (2006) [Pubmed]
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