Differential contribution of dopamine D2S and D2L receptors in the modulation of glutamate and GABA transmission in the striatum

D. Centonze, P. Gubellini, A. Usiello, S. Rossi, A. Tscherter, E. Bracci, E. Erbs, N. Tognazzi, G. Bernardi, A. Pisani, P. Calabresi, E. Borrelli

Research output: Contribution to journalArticlepeer-review

Abstract

Compelling evidence indicates that the long (D2L) and the short (D2S) isoform of dopamine (DA) D2 receptors serve distinct physiological functions in vivo. To address the involvement of these isoforms in the control of synaptic transmission in the striatum, we measured the sensitivity to D2 receptor stimulation of glutamate- and GABA-mediated currents recorded from striatal neurons of three mutant mice, in which the expression of D2L and D2S receptors was either ablated or variably altered. Our data indicate that both isoforms participate in the presynaptic inhibition of GABA transmission in the striatum, while the D2-receptor-dependent modulation of glutamate release preferentially involves the D2S receptor. Accordingly, the inhibitory effects of the DA D2 receptor agonist quinpirole (10 μM) on GABA A-mediated spontaneous inhibitory postsynaptic currents (IPSCs)correlate with the total number of D2 receptor sites in the striatum, irrespective of the specific receptor isoform expressed. In contrast, glutamate-mediated spontaneous excitatory postsynaptic currents (EPSCs) were significantly inhibited by quinpirole only when the total number of D2 receptor sites, normally composed by both D2L and D2S receptors in a ratio favoring the D2L isoform, was modified to express only the D2S isoform at higher than normal levels. Understanding the physiological roles of DA D2 receptors in the striatum is essential for the treatment of several neuropsychiatric conditions, such as Parkinson's disease, Tourette's syndrome, schizophrenia, and drug addiction.

Original languageEnglish
Pages (from-to)157-166
Number of pages10
JournalNeuroscience
Volume129
Issue number1
DOIs
Publication statusPublished - 2004

Keywords

  • basal ganglia
  • electrophysiology
  • EPSCs
  • IPSCs
  • synaptic transmission
  • transgenic mice

ASJC Scopus subject areas

  • Neuroscience(all)

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