M5 muscarinic receptors are needed for slow activation of dopamine neurons and for rewarding brain stimulation

John Yeomans, Gina Forster, Charles Blaha

Research output: Contribution to journalArticle

71 Citations (Scopus)

Abstract

Mesopontine cholinergic neurons (Ch5 and Ch6 cell groups) activate the cerebral cortex via thalamic projections, and activate locomotion and reward via dopamine neurons in the substantia nigra and ventral tegmental area (VTA). Nicotinic receptors in VTA activate dopamine neurons quickly, and are needed for the stimulant and rewarding effects of nicotine in rats. Muscarinic receptors in VTA activate dopamine neurons slowly, and are needed for the rewarding effects of hypothalamic stimulation, but do not increase locomotion. Antisense oligonucleotides targetting M5 mRNA, when infused into the VTA, inhibited M5 receptor binding and rewarding hypothalamic stimulation. Mutant mice with truncated M5 muscarinic receptor genes drank more water than wild-type controls. Spontaneous locomotion and locomotor responses to amphetamine and scopolamine were unchanged. Electrical stimulation near Ch6 induced dopamine release in the nucleus accumbens in two phases, an early phase (0-2 min after stimulation) dependent on nicotinic and gluatamatergic receptors in VTA, and a late phase (8-50 min after stimulation) dependent on muscarinic receptors in VTA. The late phase was lost in M5 mutant mice, while the early phase was unchanged. M5 muscarinic receptors bind slowly to muscarinic ligands, and appear to mediate slow secretions.

Original languageEnglish (US)
Pages (from-to)2449-2456
Number of pages8
JournalLife Sciences
Volume68
Issue number22-23
DOIs
StatePublished - Apr 27 2001

Fingerprint

Muscarinic M5 Receptors
Ventral Tegmental Area
Dopaminergic Neurons
Neurons
Dopamine
Brain
Chemical activation
Nicotinic Receptors
Muscarinic Receptors
Locomotion
Cholinergic Agents
Scopolamine Hydrobromide
Antisense Oligonucleotides
Amphetamine
Nicotine
Rats
Cholinergic Neurons
Genes
Nucleus Accumbens
Substantia Nigra

Keywords

  • Antisense oligonucleotides
  • Cholinergic
  • Chronoamperommetry
  • Locomotion
  • Mesolimbic
  • Mutants
  • Nicotinic
  • Nigrostriatal

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology, Toxicology and Pharmaceutics(all)

Cite this

M5 muscarinic receptors are needed for slow activation of dopamine neurons and for rewarding brain stimulation. / Yeomans, John; Forster, Gina; Blaha, Charles.

In: Life Sciences, Vol. 68, No. 22-23, 27.04.2001, p. 2449-2456.

Research output: Contribution to journalArticle

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