Target-specific glutamatergic regulation of dopamine neurons in the ventral tegmental area

Ryuichi Takahata, Bita Moghaddam

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to play a critical role in affective, motivational, and cognitive functioning. There are fundamental target-specific differences in the functional characteristics of subsets of these neurons. For example, DA afferents to the prefrontal cortex (PFC) have a higher firing and transmitter turnover rate and are more responsive to some pharmacological and environmental stimuli than DA projections to the nucleus accumbens (NAc), These functional differences may be attributed in part to differences in tonic regulation by glutamate. The present study provides evidence for this mechanism: In freely moving animals, blockade of basal glutamatergic activity in the VTA by the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate antagonist LY293558 produced an increase in DA release in the NAc while significantly decreasing DA release in the PFC. These data support an AMPA receptor-mediated tonic inhibitory regulation of mesoaccumbens neurons and a tonic excitatory regulation of mesoprefrontal DA neurons. This differential regulation may result in target-specific effects on the basal output of DA neurons and on the regulatory influence of voltage-gated NMDA receptors in response to phasic activation by behaviorally relevant stimuli.

Original languageEnglish (US)
Pages (from-to)1775-1778
Number of pages4
JournalJournal of Neurochemistry
Volume75
Issue number4
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Ventral Tegmental Area
Dopaminergic Neurons
Neurons
Dopamine
Nucleus Accumbens
Prefrontal Cortex
tezampanel
Isoxazoles
alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Kainic Acid
N-Methyl-D-Aspartate Receptors
Glutamic Acid
Pharmacology
Transmitters
Animals
Chemical activation
Electric potential

Keywords

  • Addiction
  • N-Methyl-D-aspartate
  • Nucleus accumbens
  • Prefrontal cortex
  • Schizophrenia
  • Stress

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Target-specific glutamatergic regulation of dopamine neurons in the ventral tegmental area. / Takahata, Ryuichi; Moghaddam, Bita.

In: Journal of Neurochemistry, Vol. 75, No. 4, 2000, p. 1775-1778.

Research output: Contribution to journalArticle

@article{7209add8a870494385989555b6d2a723,
title = "Target-specific glutamatergic regulation of dopamine neurons in the ventral tegmental area",
abstract = "Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to play a critical role in affective, motivational, and cognitive functioning. There are fundamental target-specific differences in the functional characteristics of subsets of these neurons. For example, DA afferents to the prefrontal cortex (PFC) have a higher firing and transmitter turnover rate and are more responsive to some pharmacological and environmental stimuli than DA projections to the nucleus accumbens (NAc), These functional differences may be attributed in part to differences in tonic regulation by glutamate. The present study provides evidence for this mechanism: In freely moving animals, blockade of basal glutamatergic activity in the VTA by the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate antagonist LY293558 produced an increase in DA release in the NAc while significantly decreasing DA release in the PFC. These data support an AMPA receptor-mediated tonic inhibitory regulation of mesoaccumbens neurons and a tonic excitatory regulation of mesoprefrontal DA neurons. This differential regulation may result in target-specific effects on the basal output of DA neurons and on the regulatory influence of voltage-gated NMDA receptors in response to phasic activation by behaviorally relevant stimuli.",
keywords = "Addiction, N-Methyl-D-aspartate, Nucleus accumbens, Prefrontal cortex, Schizophrenia, Stress",
author = "Ryuichi Takahata and Bita Moghaddam",
year = "2000",
doi = "10.1046/j.1471-4159.2000.0751775.x",
language = "English (US)",
volume = "75",
pages = "1775--1778",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "4",

}

TY - JOUR

T1 - Target-specific glutamatergic regulation of dopamine neurons in the ventral tegmental area

AU - Takahata, Ryuichi

AU - Moghaddam, Bita

PY - 2000

Y1 - 2000

N2 - Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to play a critical role in affective, motivational, and cognitive functioning. There are fundamental target-specific differences in the functional characteristics of subsets of these neurons. For example, DA afferents to the prefrontal cortex (PFC) have a higher firing and transmitter turnover rate and are more responsive to some pharmacological and environmental stimuli than DA projections to the nucleus accumbens (NAc), These functional differences may be attributed in part to differences in tonic regulation by glutamate. The present study provides evidence for this mechanism: In freely moving animals, blockade of basal glutamatergic activity in the VTA by the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate antagonist LY293558 produced an increase in DA release in the NAc while significantly decreasing DA release in the PFC. These data support an AMPA receptor-mediated tonic inhibitory regulation of mesoaccumbens neurons and a tonic excitatory regulation of mesoprefrontal DA neurons. This differential regulation may result in target-specific effects on the basal output of DA neurons and on the regulatory influence of voltage-gated NMDA receptors in response to phasic activation by behaviorally relevant stimuli.

AB - Dopamine (DA) neurons in the ventral tegmental area (VTA) are thought to play a critical role in affective, motivational, and cognitive functioning. There are fundamental target-specific differences in the functional characteristics of subsets of these neurons. For example, DA afferents to the prefrontal cortex (PFC) have a higher firing and transmitter turnover rate and are more responsive to some pharmacological and environmental stimuli than DA projections to the nucleus accumbens (NAc), These functional differences may be attributed in part to differences in tonic regulation by glutamate. The present study provides evidence for this mechanism: In freely moving animals, blockade of basal glutamatergic activity in the VTA by the selective α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA)/kainate antagonist LY293558 produced an increase in DA release in the NAc while significantly decreasing DA release in the PFC. These data support an AMPA receptor-mediated tonic inhibitory regulation of mesoaccumbens neurons and a tonic excitatory regulation of mesoprefrontal DA neurons. This differential regulation may result in target-specific effects on the basal output of DA neurons and on the regulatory influence of voltage-gated NMDA receptors in response to phasic activation by behaviorally relevant stimuli.

KW - Addiction

KW - N-Methyl-D-aspartate

KW - Nucleus accumbens

KW - Prefrontal cortex

KW - Schizophrenia

KW - Stress

UR - http://www.scopus.com/inward/record.url?scp=0033822584&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033822584&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.2000.0751775.x

DO - 10.1046/j.1471-4159.2000.0751775.x

M3 - Article

C2 - 10987862

AN - SCOPUS:0033822584

VL - 75

SP - 1775

EP - 1778

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 4

ER -