Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area

Forster, Gina L.; Blaha, Charles D.

doi:10.1046/j.1460-9568.2000.00250.x

Cited by 271Neurotransmitter Receptor Influence on BehaviorNeuroscience and Neuropharmacology ResearchNicotinic Acetylcholine Receptors Study

Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area

Forster, Gina L., Blaha, Charles D.·2000·European Journal of Neuroscience

DOI 10.1046/j.1460-9568.2000.00250.x

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Abstract

Cholinergic and glutamatergic neurons in the laterodorsal tegmentum (LDT) and neighbouring mesopontine nuclei are thought to influence mesolimbic dopaminergic neuronal activity involved in goal‐directed behaviours. We measured the changes in dopamine oxidation current (corresponding with dopamine efflux) in the nucleus accumbens (NAc) in response to electrical stimulation of the LDT using in vivo chronoamperometry in urethane‐anaesthetized rats. LDT stimulation (35 Hz pulse trains for 60 s, 1 s intertrain interval) evoked a three‐component change in dopamine efflux in the NAc: (i) an initial stimulation time‐locked increase in the dopamine signal above baseline, followed by (ii) an immediate decrease below baseline, and thereafter by (iii) a prolonged increase in the dopamine signal above baseline. Intra‐VTA infusion of the nicotinic receptor antagonist mecamylamine (5 μg/0.5 μL) or the ionotropic glutamate receptor antagonist kynurenate (10 μg/μL) attenuated the first LDT‐elicited component. The second suppressive component was abolished by intra‐LDT infusions of either the nonselective or the M2‐selective muscarinic receptor antagonists scopolamine (100 μg/μL) and methoctramine (50 μg/μL), respectively. In contrast, intra‐VTA infusions of scopolamine (200 μg/μL) resulted in a selective attenuation of the third facilitatory component, whereas both second and third components were abolished by systemic injections of scopolamine (5 mg/kg). These results suggest that the initial increase, subsequent decrease, and final prolonged increase in extracellular dopamine levels in the NAc are selectively mediated by LDT‐elicited activation of (i) nicotinic and glutamatergic receptors in the VTA, (ii) muscarinic M2 autoreceptors on LDT cell bodies, and (iii) muscarinic receptors in the VTA, respectively.

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Both muscarinic and nicotinic ACh receptors are present on VTA dopamine neurons, as well as on cholinergic and glutamatergic terminals regulating different aspects of dopamine release in output sites such as the striatum and NAc.
“Both muscarinic and nicotinic ACh receptors are present on VTA dopamine neurons, as well as on cholinergic and glutamatergic terminals regulating different aspects of dopamine release in output sites, such as the striatum and NAc [160–162].”
From Adolescent nicotine exposure and persistent neurocircuitry changes: unveiling lifelong psychiatric risks (2025) · cites this paper as [161]

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Authors: Forster, G. L., & Blaha, C. D.
Affiliations: Macquarie University (AU)
Corresponding author: Blaha, Charles D.
ORCID: Forster, Gina L.
Blaha, Charles D.
Venue: European Journal of Neuroscience
Publisher: Wiley
Published: 2000-10
Volume: 12
Issue: 10
Pages: 3596-3604
ISSN: 0953-816X (ISSN-L)
1460-9568
DOI: 10.1046/j.1460-9568.2000.00250.x
OpenAlex: W2037683196
Cited by: 271
References: 81
Citations by year: 2026: 4 · 2025: 5 · 2024: 11 · 2023: 5 · 2022: 10 · 2021: 4 · 2020: 22 · 2019: 9 · 2018: 6 · 2017: 8 · 2016: 8 · 2015: 11 · 2014: 18 · 2013: 12 · 2012: 11
FWCI: 3.49
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 449 d)
Locations: European Journal of Neuroscience (publishedVersion)
PubMed (publishedVersion)
Funders: Macquarie University
University of Adelaide
Australian Research Council
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nicotinic Acetylcholine Receptors Study
Keywords: laterodorsal tegmentum, nucleus accumbens, dopamine efflux, ventral tegmental area, nicotinic acetylcholine receptors, M2 muscarinic receptor, glutamate receptors, mesolimbic dopamine system, mecamylamine, kynurenic acid, scopolamine, methoctramine, goal-directed behavior
MeSH terms: Animals, Cholinergic Fibers, Diamines, Dopamine, Electric Stimulation, Kynurenic Acid, Male, Mecamylamine, Neural Pathways, Neurons, Nucleus Accumbens, Parasympatholytics, Pons, Receptors, Cholinergic, Receptors, Muscarinic, Receptors, Nicotinic, Scopolamine, Stereotaxic Techniques, Rats, Wistar, Receptors, Glutamate, Ventral Tegmental Area, Rats

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Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area

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