Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons

Diego Centonze, Cristina Grande, Alessandro Usiello, Paolo Gubellini, Eric Erbs, Ana B. Martín, Antonio Pisani, Nadia Tognazzi, Giorgio Bernardi, Rosario Moratalla, Emiliana Borrelli, Paolo Calabresi

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Abstract

By stimulating distinct receptor subtypes, dopamine (DA) exerts presynaptic and postsynaptic actions on both large aspiny (LA) cholinergic and fast-spiking (FS) parvalbumin-positive interneurons of the striatum. Lack of receptor- and isoform-specific pharmacological agents, however, has hampered the progress toward a detailed identification of the specific DA receptors involved in these actions. To overcome this issue, in the present study we used four different mutant mice in which the expression of specific DA receptors was ablated. In D1 receptor null mice, DIR-/-, DA dose-dependently depolarized both LA and FS interneurons. Interestingly, SCH 233390 (10 μM), a D1-like (D1 and D5) receptor antagonist, but not L-sulpiride (3-10 μM), a D2-like (D2, D3, D4) receptor blocker, prevented this effect, implying D5 receptors in this action. Accordingly, immunohistochemical analyses in both wild-type and D1R-/- mice confirmed the expression of D5 receptors in both cholinergic and parvalbumin-positive interneurons of the striatum. In mice lacking D2 receptors, D2R-/-, the DA-dependent inhibition of GABA transmission was lost in both interneuron populations. Both isoforms of D2 receptor, D2L and D2S, were very likely involved in this inhibitory action, as revealed by the electrophysiological analysis of the effect of the DA D2-like receptor agonist quinpirole in two distinct mutants lacking D2L receptors and expressing variable contents of D2S receptors. The identification of the receptor subtypes involved in the actions of DA on different populations of striatal cells is essential to understand the circuitry of the basal ganglia and to develop pharmacological strategies able to interfere selectively with specific neuronal functions.

Original languageEnglish
Pages (from-to)6245-6254
Number of pages10
JournalJournal of Neuroscience
Volume23
Issue number15
Publication statusPublished - Jul 16 2003

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Keywords

  • Basal ganglia
  • D1 receptors
  • D2L receptors
  • D2S receptors
  • Electrophysiology
  • GABA transmission
  • Mutant mice

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Centonze, D., Grande, C., Usiello, A., Gubellini, P., Erbs, E., Martín, A. B., Pisani, A., Tognazzi, N., Bernardi, G., Moratalla, R., Borrelli, E., & Calabresi, P. (2003). Receptor subtypes involved in the presynaptic and postsynaptic actions of dopamine on striatal interneurons. Journal of Neuroscience, 23(15), 6245-6254.