Knocking out the dopamine reuptake transporter (DAT) does not change the baseline brain arachidonic acid signal in the mouse

Epolia Ramadan, Lisa Chang, Mei Chen, Kaizong Ma, F. Scott Hall, George R. Uhl, Stanley I. Rapoport, Mireille Basselin

Research output: Contribution to journalArticle

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- 14C]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.

Original languageEnglish (US)
Pages (from-to)373-380
Number of pages8
JournalInternational Journal of Neuroscience
Volume122
Issue number7
DOIs
StatePublished - Jul 2012
Externally publishedYes

Keywords

  • arachidonic acid
  • dopamine
  • dopamine transporter
  • knockout
  • mouse
  • phospholipase A

ASJC Scopus subject areas

  • Neuroscience(all)

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