Effect of MPTP-induced denervation on basal ganglia GABAB receptors: Correlation with dopamine concentrations and dopamine transporter

Frédéric Calon, Nadia Lavertu, Anne Marie Lemieux, Marc Morissette, Martin Goulet, Richard Grondin, Pierre J. Blanchet, Paul J. Bédard, Thérèse Di Paolo

Research output: Contribution to journalArticlepeer-review

32 Scopus citations


We investigated the effect of MPTP-induced lesion of the substantia nigra pars compacta (SNpc) dopaminergic neurons on GABAB receptors in the basal ganglia of mice and monkeys using receptor autoradiography and in situ hybridization. The extent of the lesion was measured with striatal catecholamine content, striatal binding of 125I-RTI-121 to dopamine transporter (DAT), and DAT expression in the SNpc. GABAB receptors in mice brain were evaluated using 3H-CGP54626 and its expression was measured with oligonucleotides probes targeting the mRNAs of GABAB(1a+b), GABAB(1a), GABAB(1b), GABAB(2) subunits. In monkeys, 125I-CGP64213 and selective probes for GABAB(1a+b) and GABAB(2) mRNAs were used. In mice, dopamine content, 125I-RTI-121 binding, and DAT expression were reduced by 44%, 40%, and 39% after a dose of 40 mg/kg of MPTP and 74%, 70%, and 34% after 120 mg/kg of MPTP, respectively. In monkeys, dopamine content and DAT expression were decreased by more than 90% and 80%, respectively. In the striatum and the subthalamic nucleus, GABAB receptors were unchanged following MPTP in both species. In the SNpc of mice, MPTP (120 mg/kg) induced a significant decrease of 3H-CGP54626 binding (-10%) and of the expression of GABAB(1a+b) mRNA (-13%). The decrease of the expression of GABAB(1a+b) mRNA was correlated with dopamine content, 125I-RTI-121 binding and DAT expression. In MPTP-treated monkeys, 125I-CGP64213 binding (-40%), GABAB(1a+b) mRNA (-69%) and GABAB(2) mRNA (-66%) were also significantly decreased in the SNpc. Our results suggest that MPTP-induced denervation is associated with a decrease of GABAB receptors restricted to the SNpc. These observations may be relevant to the pathophysiology of motor disorders involving dysfunction of the basal ganglia such as Parkinson disease.

Original languageEnglish
Pages (from-to)225-234
Number of pages10
Issue number3
StatePublished - Jun 1 2001


  • Autoradiography
  • Dopamine
  • GABA
  • In situ hybridization
  • Parkinson
  • Substantia nigra

ASJC Scopus subject areas

  • Cellular and Molecular Neuroscience


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