Muscarinic and dopaminergic receptor subtypes on striatal cholinergic interneurons

Valina L. Dawson, Ted M. Dawson, James K. Wamsley

Research output: Contribution to journalArticlepeer-review

Abstract

Unilateral stereotaxic injection of small amounts of the cholinotoxin, AF64A, caused minimal nonselective tissue damage and resulted in a significant loss of the presynaptic cholinergic markers [3H]hemicholinium-3 (45% reduction) and choline acetyltransferase (27% reduction). No significant change from control was observed in tyrosine hydroxylase or tryptophan hydroxylase activity; presynaptic neuronal markers for dopamine- and serotonin-containing neurons, respectively. The AF64A lesion resulted in a significant reduction of dopamine D2 receptors as evidenced by a decrease in [3H]sulpiride binding (42% reduction) and decrease of muscarinic non-M1 receptors as shown by a reduction in [3H]QNB binding in the presence of 100 nM pirenzepine (36% reduction). Saturation studies revealed that the change in [3H]sulpiride and [3H]QNB binding was due to a change in Bmax not Kd. Intrastriatal injection of AF64A failed to alter dopamine D1 or muscarinic M1 receptors labeled with [3H]SCH23390 and[3H]pirenzepine, respectively. In addition, no change in [3H]forskolin-labeled adenylate cyclase was observed. These results demonstrate that a subpopulation of muscarinic receptors (non-M1) are presynaptic on cholinergic interneurons (hence, autoreceptors), and a subpopulation of dopamine D2 receptors are postsynaptic on cholinergic interneurons. Furthermore, dopamine D1, muscarinic M1 and [3H]forskolin-labeled adenylate cyclase are not localized to striatal cholinergic interneurons.

Original languageEnglish (US)
Pages (from-to)903-912
Number of pages10
JournalBrain Research Bulletin
Volume25
Issue number6
DOIs
StatePublished - Dec 1990
Externally publishedYes

Keywords

  • AF64A
  • Acetylcholine
  • Autoreceptors
  • Cholinotoxin
  • D receptors
  • D receptors
  • Dopamine receptor subtypes
  • Hemicholinium-3 binding
  • M receptors
  • Muscarinic receptor subtypes
  • Non-M receptors

ASJC Scopus subject areas

  • Neuroscience(all)

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