Midbrain muscarinic receptors modulate morphine-induced accumbal and striatal dopamine efflux in the rat

A. D. Miller, Gina L Forster, J. S. Yeomans, C. D. Blaha

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Midbrain dopamine neurons are critical in mediating the rewarding effects of opiates in dependent rats, as well as modulating some manifestations of opiate withdrawal. Morphine is known to excite dopamine neurons and thereby facilitate forebrain dopamine transmission through inhibition of GABA neurons. Cholinergic neurons in the mesopontine laterodorsal and pedunculopontine tegmental nuclei provide the principal source of excitatory cholinergic input to ventral tegmental area and substantia nigra pars compacta dopamine-containing neurons, via actions on midbrain muscarinic and nicotinic acetylcholine receptors. The present study hypothesized that a reduction in tonic cholinergic input via blockade of midbrain muscarinic receptors would reduce the pharmacological effects of morphine on forebrain dopamine release. Using in vivo chronoamperometry, alterations in morphine-evoked dopamine efflux were monitored at stearate-graphite paste electrodes implanted unilaterally in the nucleus accumbens and striatum of urethane (1.5g/kg) anesthetized rats, following the pharmacological inhibition of ventral tegmental area/substantia nigra pars compacta muscarinic receptors. The facilitatory effects of morphine (2.0mg/kg, i.v.) on accumbens and striatal dopamine efflux were markedly reduced by prior infusion of the non-selective muscarinic receptor antagonist scopolamine (200μg/μl) into the ventral tegmental area or substantia nigra pars compacta, respectively. These findings demonstrate that decreased activation of midbrain muscarinic receptors attenuates the excitatory effects of morphine on mesoaccumbens and nigrostriatal dopaminergic transmission.

Original languageEnglish (US)
Pages (from-to)531-538
Number of pages8
JournalNeuroscience
Volume136
Issue number2
DOIs
StatePublished - Nov 21 2005

Fingerprint

Corpus Striatum
Muscarinic Receptors
Mesencephalon
Morphine
Dopamine
Ventral Tegmental Area
Opiate Alkaloids
Dopaminergic Neurons
Prosencephalon
Cholinergic Agents
Pedunculopontine Tegmental Nucleus
Pharmacology
Stearates
GABAergic Neurons
Implanted Electrodes
Cholinergic Neurons
Muscarinic Antagonists
Scopolamine Hydrobromide
Graphite
Urethane

Keywords

  • Acetylcholine
  • Chronoamperometry
  • Mesopontine
  • Scopolamine
  • Substantia nigra
  • Ventral tegmental area

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Midbrain muscarinic receptors modulate morphine-induced accumbal and striatal dopamine efflux in the rat. / Miller, A. D.; Forster, Gina L; Yeomans, J. S.; Blaha, C. D.

In: Neuroscience, Vol. 136, No. 2, 21.11.2005, p. 531-538.

Research output: Contribution to journalArticle

Miller, A. D. ; Forster, Gina L ; Yeomans, J. S. ; Blaha, C. D. / Midbrain muscarinic receptors modulate morphine-induced accumbal and striatal dopamine efflux in the rat. In: Neuroscience. 2005 ; Vol. 136, No. 2. pp. 531-538.
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