Using metabotropic glutamate receptors to modulate cocaine's synaptic and behavioral effects

MGluR1 finds a niche

Jessica A. Loweth, Kuei Y. Tseng, Marina Wolf

Research output: Contribution to journalReview article

26 Citations (Scopus)

Abstract

Group I metabotropic glutamate receptors (mGluR) are important modulators of excitatory synaptic transmission and therefore potential targets for drug development. In several brain regions (ventral tegmental area (VTA), cerebellum, and amygdala), stimulation of mGluR1 selectively inhibits synaptic transmission mediated by calcium-permeable AMPA receptors (CP-AMPARs) and thus produces synaptic depression. The same relationship has now been demonstrated in the nucleus accumbens (NAc), a region that is critical for cocaine craving. CP-AMPAR levels in NAc synapses are normally low, but they increase after prolonged withdrawal from extended-access cocaine self-administration (SA). These CP-AMPARs mediate the intensified ('incubated') cue-induced cocaine craving observed under these conditions. Therefore, activation of mGluR1 with positive allosteric modulators (PAM) may reduce cue-induced relapse in abstinent cocaine addicts.

Original languageEnglish (US)
Pages (from-to)500-506
Number of pages7
JournalCurrent Opinion in Neurobiology
Volume23
Issue number4
DOIs
StatePublished - Aug 1 2013
Externally publishedYes

Fingerprint

Metabotropic Glutamate Receptors
Cocaine
AMPA Receptors
Nucleus Accumbens
Calcium
Synaptic Transmission
Cues
Ventral Tegmental Area
Self Administration
Amygdala
Synapses
Cerebellum
Recurrence
metabotropic glutamate receptor type 1
Brain
Pharmaceutical Preparations
Craving

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Using metabotropic glutamate receptors to modulate cocaine's synaptic and behavioral effects : MGluR1 finds a niche. / Loweth, Jessica A.; Tseng, Kuei Y.; Wolf, Marina.

In: Current Opinion in Neurobiology, Vol. 23, No. 4, 01.08.2013, p. 500-506.

Research output: Contribution to journalReview article

@article{48b3fdea1220405ebbff5ed06c3e69bf,
title = "Using metabotropic glutamate receptors to modulate cocaine's synaptic and behavioral effects: MGluR1 finds a niche",
abstract = "Group I metabotropic glutamate receptors (mGluR) are important modulators of excitatory synaptic transmission and therefore potential targets for drug development. In several brain regions (ventral tegmental area (VTA), cerebellum, and amygdala), stimulation of mGluR1 selectively inhibits synaptic transmission mediated by calcium-permeable AMPA receptors (CP-AMPARs) and thus produces synaptic depression. The same relationship has now been demonstrated in the nucleus accumbens (NAc), a region that is critical for cocaine craving. CP-AMPAR levels in NAc synapses are normally low, but they increase after prolonged withdrawal from extended-access cocaine self-administration (SA). These CP-AMPARs mediate the intensified ('incubated') cue-induced cocaine craving observed under these conditions. Therefore, activation of mGluR1 with positive allosteric modulators (PAM) may reduce cue-induced relapse in abstinent cocaine addicts.",
author = "Loweth, {Jessica A.} and Tseng, {Kuei Y.} and Marina Wolf",
year = "2013",
month = "8",
day = "1",
doi = "10.1016/j.conb.2013.01.009",
language = "English (US)",
volume = "23",
pages = "500--506",
journal = "Current Opinion in Neurobiology",
issn = "0959-4388",
publisher = "Elsevier Limited",
number = "4",

}

TY - JOUR

T1 - Using metabotropic glutamate receptors to modulate cocaine's synaptic and behavioral effects

T2 - MGluR1 finds a niche

AU - Loweth, Jessica A.

AU - Tseng, Kuei Y.

AU - Wolf, Marina

PY - 2013/8/1

Y1 - 2013/8/1

N2 - Group I metabotropic glutamate receptors (mGluR) are important modulators of excitatory synaptic transmission and therefore potential targets for drug development. In several brain regions (ventral tegmental area (VTA), cerebellum, and amygdala), stimulation of mGluR1 selectively inhibits synaptic transmission mediated by calcium-permeable AMPA receptors (CP-AMPARs) and thus produces synaptic depression. The same relationship has now been demonstrated in the nucleus accumbens (NAc), a region that is critical for cocaine craving. CP-AMPAR levels in NAc synapses are normally low, but they increase after prolonged withdrawal from extended-access cocaine self-administration (SA). These CP-AMPARs mediate the intensified ('incubated') cue-induced cocaine craving observed under these conditions. Therefore, activation of mGluR1 with positive allosteric modulators (PAM) may reduce cue-induced relapse in abstinent cocaine addicts.

AB - Group I metabotropic glutamate receptors (mGluR) are important modulators of excitatory synaptic transmission and therefore potential targets for drug development. In several brain regions (ventral tegmental area (VTA), cerebellum, and amygdala), stimulation of mGluR1 selectively inhibits synaptic transmission mediated by calcium-permeable AMPA receptors (CP-AMPARs) and thus produces synaptic depression. The same relationship has now been demonstrated in the nucleus accumbens (NAc), a region that is critical for cocaine craving. CP-AMPAR levels in NAc synapses are normally low, but they increase after prolonged withdrawal from extended-access cocaine self-administration (SA). These CP-AMPARs mediate the intensified ('incubated') cue-induced cocaine craving observed under these conditions. Therefore, activation of mGluR1 with positive allosteric modulators (PAM) may reduce cue-induced relapse in abstinent cocaine addicts.

UR - http://www.scopus.com/inward/record.url?scp=84881098363&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84881098363&partnerID=8YFLogxK

U2 - 10.1016/j.conb.2013.01.009

DO - 10.1016/j.conb.2013.01.009

M3 - Review article

VL - 23

SP - 500

EP - 506

JO - Current Opinion in Neurobiology

JF - Current Opinion in Neurobiology

SN - 0959-4388

IS - 4

ER -