Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice

Timothy E. Koeltzow, Ming Xu, Donald C. Cooper, Xiu Ti Hu, Susumu Tonegawa, Marina E. Wolf, Francis J. White

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Abstract

Dopamine (DA) autoreceptors expressed along the somatodendritic extent of midbrain DA neurons modulate impulse activity, whereas those expressed at DA nerve terminals regulate both DA synthesis and release. Considerable evidence has indicated that these DA autoreceptors are of the D2 subtype of DA receptors. However, many pharmacological studies have suggested an autoreceptor role for the DA D3 receptor. This possibility was tested with mice lacking the D3 receptor as a result of gene targeting. The basal firing rates of DA neurons within both the substantia nigra and ventral tegmental area were not different in D3 receptor mutant and wild-type mice. The putative D3 receptor-selective agonist R(+)-trans-3,4,4a, 10b-tetrahydro-4- propyl-2H, 5H-(1)benzopyrano(4,3-b)-1,4-oxazin-9-ol (PD 128907) was equipotent at inhibiting the activity of both populations of midbrain DA neurons in the two groups of mice. In the χ-butyrolactone (GBL) model of DA autoreceptor function, mutant and wild-type mice were identical with respect to striatal DA synthesis and its suppression by PD 128907. In vivo microdialysis studies of DA release in ventral striatum revealed higher basal levels of extracellular DA in mutant mice but similar inhibitory effects of PD 128907 in mutant and wildtype mice. These results suggest that the effects of PD 128907 on dopamine cell function reflect stimulation of D2 as opposed to D3 receptors. Although D3 receptors do not seem to be significantly involved in DA autoreceptor function, they may participate in postsynaptically activated short-loop feedback modulation of DA release.

Original languageEnglish (US)
Pages (from-to)2231-2238
Number of pages8
JournalJournal of Neuroscience
Volume18
Issue number6
StatePublished - Mar 15 1998

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Keywords

  • D receptors
  • Dopamine autoreceptors
  • Dopamine neurons
  • Dopamine receptors
  • Dopamine release
  • Dopamine synthesis
  • Mutant mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Koeltzow, T. E., Xu, M., Cooper, D. C., Hu, X. T., Tonegawa, S., Wolf, M. E., & White, F. J. (1998). Alterations in dopamine release but not dopamine autoreceptor function in dopamine D3 receptor mutant mice. Journal of Neuroscience, 18(6), 2231-2238.