title: Knocking out the dopamine reuptake transporter (DAT) does not change the baseline brain arachidonic acid signal in the mouse.
abstract: BACKGROUND
  Dopamine transporter (DAT) homozygous knockout (DAT(-/-)) mice have a 10-fold higher extracellular (DA) concentration in the caudate-putamen and nucleus accumbens than do wildtype (DAT(+/+)) mice, but show reduced presynaptic DA synthesis and fewer postsynaptic D(2) receptors. One aspect of neurotransmission involves DA binding to postsynaptic D(2)-like receptors coupled to cytosolic phospholipase A(2) (cPLA(2)), which releases the second messenger, arachidonic acid (AA), from synaptic membrane phospholipid. We hypothesized that tonic overactivation of D(2)-like receptors in DAT(-/-) mice due to the excess DA would not increase brain AA signaling, because of compensatory downregulation of postsynaptic DA signaling mechanisms.
  
  
  METHODS
  [1-(14)C]AA was infused intravenously for 3 min in unanesthetized DAT(+/+), heterozygous (DAT(+/-)), and DAT(-/-) mice. AA incorporation coefficients k* and rates J(in), markers of AA metabolism and signaling, were imaged in 83 brain regions using quantitative autoradiography; brain cPLA(2)-IV activity also was measured.
  
  
  RESULTS
  Neither k* nor J(in) for AA in any brain region, or brain cPLA(2)-IV activity, differed significantly among DAT(-/-), DAT(+/-), and DAT(+/+) mice.
  
  
  CONCLUSIONS
  These results differ from reported increases in k* and J(in) for AA, and in brain cPLA(2) expression, in serotonin reuptake transporter (5-HTT) knockout mice, and suggest that postsynaptic dopaminergic neurotransmission mechanisms involving AA are downregulated despite elevated DA in DAT(-/-) mice.
authors.affiliation: Brain Physiology and Metabolism Section, National Institute on Aging, National Institutes of Health, Bethesda, MD 20892, USA. ramadanir@mail.nih.gov
authors.forename: Epolia
authors.initials: E
authors.lastname: Ramadan
authors.forename: Lisa
authors.initials: L
authors.lastname: Chang
authors.forename: Mei
authors.initials: M
authors.lastname: Chen
authors.forename: Kaizong
authors.initials: K
authors.lastname: Ma
authors.forename: F Scott
authors.initials: FS
authors.lastname: Hall
authors.forename: George R
authors.initials: GR
authors.lastname: Uhl
authors.forename: Stanley I
authors.initials: SI
authors.lastname: Rapoport
authors.forename: Mireille
authors.initials: M
authors.lastname: Basselin
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D001345:Autoradiography; D001835:Body Weight / Q000235:genetics; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D001931:Brain Mapping; D002247:Carbon Isotopes / Q000378:metabolism; D050483:Dopamine Plasma Membrane Transport Proteins / Q000172:deficiency*; D015536:Down-Regulation / Q000235:genetics; D005227:Fatty Acids / Q000097:blood; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D054467:Phospholipases A2; D011188:Potassium / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D002247:Carbon Isotopes; D050483:Dopamine Plasma Membrane Transport Proteins; D005227:Fatty Acids; D016718:Arachidonic Acid; D054467:Phospholipases A2; D011188:Potassium