title: Imaging apomorphine stimulation of brain arachidonic acid signaling via D2-like receptors in unanesthetized rats.
abstract: 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.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. abeshb@mail.nih.gov
authors.forename: Abesh Kumar
authors.initials: AK
authors.lastname: Bhattacharjee
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Laura
authors.initials: L
authors.lastname: White
authors.forename: Richard P
authors.initials: RP
authors.lastname: Bazinet
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
mesh_terms: 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*
chemical_list: 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