D-Amphetamine stimulates D2 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.
Bhattacharjee
Abesh K
AK
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, Maryland 20892, USA. abeshb@mail.nih.gov
Chang
Lisa
L
White
Laura
L
Bazinet
Richard P
RP
Rapoport
Stanley I
SI
D000465:Algorithms; D000818:Animals; D016718:Arachidonic Acid / Q000493:pharmacokinetics / Q000502:physiology*; D001345:Autoradiography; D003913:Dextroamphetamine / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D018765:Dopamine Uptake Inhibitors / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D008297:Male; D009714:Nucleus Accumbens / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D015398:Signal Transduction / Q000187:drug effects*
D018492:Dopamine Antagonists; D018765:Dopamine Uptake Inhibitors; D012333:RNA, Messenger; D017448:Receptors, Dopamine D2; D016718:Arachidonic Acid; D020891:Raclopride; D005947:Glucose; D003913:Dextroamphetamine