Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens

Feng Zhou, Bruce Anthony, Kenneth Dunn, W. Brent Lindquist, Zao C. Xu, Ping Deng

Research output: Contribution to journalArticle

72 Citations (Scopus)

Abstract

Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology - thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes - in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.

Original languageEnglish
Pages (from-to)148-161
Number of pages14
JournalBrain Research
Volume1134
Issue number1
DOIs
StatePublished - Feb 23 2007

Fingerprint

Dendritic Spines
Nucleus Accumbens
Reward
Alcohol Drinking
Alcohols
Brain
Spine
Glutamic Acid
Dendrites
Alcoholism
N-Methyl-D-Aspartate Receptors
Photons
Astrocytes
Drinking
Microscopy
Exons
Protein Isoforms
Western Blotting
History
Head

Keywords

  • Addiction
  • Extended amygdala
  • GABA
  • Genetics
  • Glutamate
  • Medium spiny neuron
  • NMDA
  • P rat
  • Postsynaptic
  • Repeated deprivation
  • Two-photon laser microscopy

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

Cite this

Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens. / Zhou, Feng; Anthony, Bruce; Dunn, Kenneth; Lindquist, W. Brent; Xu, Zao C.; Deng, Ping.

In: Brain Research, Vol. 1134, No. 1, 23.02.2007, p. 148-161.

Research output: Contribution to journalArticle

Zhou, Feng ; Anthony, Bruce ; Dunn, Kenneth ; Lindquist, W. Brent ; Xu, Zao C. ; Deng, Ping. / Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens. In: Brain Research. 2007 ; Vol. 1134, No. 1. pp. 148-161.
@article{cf22b160eef948a49c3e94e97c66661a,
title = "Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens",
abstract = "Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology - thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes - in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.",
keywords = "Addiction, Extended amygdala, GABA, Genetics, Glutamate, Medium spiny neuron, NMDA, P rat, Postsynaptic, Repeated deprivation, Two-photon laser microscopy",
author = "Feng Zhou and Bruce Anthony and Kenneth Dunn and Lindquist, {W. Brent} and Xu, {Zao C.} and Ping Deng",
year = "2007",
month = "2",
day = "23",
doi = "10.1016/j.brainres.2006.11.046",
language = "English",
volume = "1134",
pages = "148--161",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Chronic alcohol drinking alters neuronal dendritic spines in the brain reward center nucleus accumbens

AU - Zhou, Feng

AU - Anthony, Bruce

AU - Dunn, Kenneth

AU - Lindquist, W. Brent

AU - Xu, Zao C.

AU - Deng, Ping

PY - 2007/2/23

Y1 - 2007/2/23

N2 - Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology - thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes - in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.

AB - Alcohol is known to affect glutamate transmission. However, how chronic alcohol affects the synaptic structure mediating glutamate transmission is unknown. Repeated alcohol exposure in a subject with familial alcoholic history often leads to alcohol addiction. The current study adopts alcohol-preferring rats, which are known to develop high drinking. Two-photon microscopy analysis indicates that chronic alcohol of 14 weeks either, under continuous alcohol (C-Alc) or with repeated deprivation (RD-Alc), causes dysmorphology - thickened, beaded, and disoriented dendrites that are reminiscent of reactive astrocytes - in a subpopulation of medium spiny neurons. The density of dendritic spines was found differentially lower in the nucleus accumbens of RD-Alc and C-Alc groups as compared with those of Water groups. Large-sized spines and multiple-headed spines were increased in the RD-Alc group. The NMDA receptor subunit NR1 proteins, as analyzed with Western blot, were upregulated in C-Alc, but not in RD-Alc. The upregulated NMDA receptor subunits of NR1 however, are predominantly a splice variant isoform with truncated exon 21, which is required for membrane-bound trafficking or anchoring into a spine synaptic site. These maladaptations may contribute to the transformation of spines. The changes, in density and head-size of spines and the corresponding NMDA receptors, demonstrated an alteration of microcircuitry for glutamate reception. The current study demonstrates for the first time that chronic alcohol exposure causes structural alteration of dendrites and their spines in the key reward brain region in animals that have a genetic background leading to alcohol addiction.

KW - Addiction

KW - Extended amygdala

KW - GABA

KW - Genetics

KW - Glutamate

KW - Medium spiny neuron

KW - NMDA

KW - P rat

KW - Postsynaptic

KW - Repeated deprivation

KW - Two-photon laser microscopy

UR - http://www.scopus.com/inward/record.url?scp=33846345905&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33846345905&partnerID=8YFLogxK

U2 - 10.1016/j.brainres.2006.11.046

DO - 10.1016/j.brainres.2006.11.046

M3 - Article

C2 - 17198693

AN - SCOPUS:33846345905

VL - 1134

SP - 148

EP - 161

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -