Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors

Juan Ji An, Mi Hyun Bae, Sang Rae Cho, Soo Hyun Lee, Seong Hoon Choi, Bae Hwan Lee, Hee Sup Shin, Yong Nyun Kim, Kye Won Park, Emiliana Borrelli, Ja Hyun Baik

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20 Citations (Scopus)

Abstract

The levels of glutamic acid decarboxylase (GAD) were strongly increased in the cortex and the striatum in dopamine D2 receptors null (D2R-/-) mice, which show a significant locomotor impairment. In this study, the effects of different GABAergic drugs on locomotor activity were analyzed in D2R-/- mice. After administering muscimol (1 mg/kg), a GABAA receptor agonist, the D2R-/- mice showed increased locomotor activity up to 200%. When the muscimol dose was increased (4-6 mg/kg), the D2R-/- mice exhibited seizure-like behavior, and the electroencephalographic (EEG) recordings during these behaviors showed a high amplitude rhythmic epileptiform activity in these mice. In situ hybridization showed that after injecting muscimol in the D2R-/- mice, the expression of enkephalin and immediate early gene, NGFI-A, was closely regulated with the locomotor activity regulated by GABAergic stimulation. These results suggest that the absence of D2R alters the GABAergic neurotransmission, specifically on GABAA-receptor mediated signaling, and stimulating the GABAA receptor can reverse the dysfunction of GABAergic inhibition in the motor circuits in the basal ganglia.

Original languageEnglish
Pages (from-to)732-741
Number of pages10
JournalMolecular and Cellular Neuroscience
Volume25
Issue number4
DOIs
Publication statusPublished - 2004 Apr 1

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience
  • Cell Biology

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  • Cite this

    An, J. J., Bae, M. H., Cho, S. R., Lee, S. H., Choi, S. H., Lee, B. H., Shin, H. S., Kim, Y. N., Park, K. W., Borrelli, E., & Baik, J. H. (2004). Altered GABAergic neurotransmission in mice lacking dopamine D2 receptors. Molecular and Cellular Neuroscience, 25(4), 732-741. https://doi.org/10.1016/j.mcn.2003.12.010