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

G. L. Forster, C. D. Blaha

Research output: Contribution to journalArticle

180 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)3596-3604
Number of pages9
JournalEuropean Journal of Neuroscience
Volume12
Issue number10
DOIs
StatePublished - Jan 1 2000

Fingerprint

Ventral Tegmental Area
Nucleus Accumbens
Glutamate Receptors
Cholinergic Receptors
Dopamine
Scopolamine Hydrobromide
Nicotinic Receptors
Nicotinic Antagonists
Kynurenic Acid
Mecamylamine
Ionotropic Glutamate Receptors
Autoreceptors
Excitatory Amino Acid Antagonists
Cholinergic Neurons
Muscarinic Antagonists
Urethane
Muscarinic Receptors
Cholinergic Agents
Electric Stimulation
Injections

Keywords

  • Chronoamperometry
  • Electrical stimulation
  • Mesopontine
  • Muscarinic receptors
  • Nicotinic receptors

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

@article{2d1f78990dc94c64995097ca76464859,
title = "Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area",
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.",
keywords = "Chronoamperometry, Electrical stimulation, Mesopontine, Muscarinic receptors, Nicotinic receptors",
author = "Forster, {G. L.} and Blaha, {C. D.}",
year = "2000",
month = "1",
day = "1",
doi = "10.1046/j.1460-9568.2000.00250.x",
language = "English (US)",
volume = "12",
pages = "3596--3604",
journal = "European Journal of Neuroscience",
issn = "0953-816X",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Laterodorsal tegmental stimulation elicits dopamine efflux in the rat nucleus accumbens by activation of acetylcholine and glutamate receptors in the ventral tegmental area

AU - Forster, G. L.

AU - Blaha, C. D.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - 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.

AB - 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.

KW - Chronoamperometry

KW - Electrical stimulation

KW - Mesopontine

KW - Muscarinic receptors

KW - Nicotinic receptors

UR - http://www.scopus.com/inward/record.url?scp=0033794295&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033794295&partnerID=8YFLogxK

U2 - 10.1046/j.1460-9568.2000.00250.x

DO - 10.1046/j.1460-9568.2000.00250.x

M3 - Article

C2 - 11029630

AN - SCOPUS:0033794295

VL - 12

SP - 3596

EP - 3604

JO - European Journal of Neuroscience

JF - European Journal of Neuroscience

SN - 0953-816X

IS - 10

ER -