Imaging apomorphine stimulation of brain arachidonic acid signaling via D2-like receptors in unanesthetized rats.
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 D1-D2 receptor agonist apomorphine may allow us to do this, as the D2-like receptor is reported to be coupled to cytosolic phospholipase A2 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 D2/D3 receptor antagonist. [1-14C]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 D1-D2 receptor agonist, apomorphine, increased the AA signal by activating only D2-like receptors in brain circuits containing regions with high D2-like receptor densities. Thus, apomorphine might be used with positron emission tomography to image brain D2-like receptor-mediated AA signaling in humans in health and disease.
Bhattacharjee
Abesh Kumar
AK
Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. abeshb@mail.nih.gov
Chang
Lisa
L
White
Laura
L
Bazinet
Richard P
RP
Rapoport
Stanley I
SI
D000818:Animals; D001058:Apomorphine / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D001345:Autoradiography; D001921:Brain / Q000187:drug effects*; D001931:Brain Mapping; D002250:Carbon Radioisotopes; D018491:Dopamine Agonists / Q000494:pharmacology*; D018492:Dopamine Antagonists / Q000494:pharmacology; D054513:Group IV Phospholipases A2 / Q000378:metabolism*; D008297:Male; D020891:Raclopride / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects*
D002250:Carbon Radioisotopes; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D017448:Receptors, Dopamine D2; D016718:Arachidonic Acid; D020891:Raclopride; D054513:Group IV Phospholipases A2; D001058:Apomorphine