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.
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. imce100@iupui.edu
authors.forename: Feng C
authors.initials: FC
authors.lastname: Zhou
authors.forename: Bruce
authors.initials: B
authors.lastname: Anthony
authors.forename: Kenneth W
authors.initials: KW
authors.lastname: Dunn
authors.forename: W Brent
authors.initials: WB
authors.lastname: Lindquist
authors.forename: Zao C
authors.initials: ZC
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Deng
mesh_terms: D020268:Alcohol-Induced Disorders, Nervous System / Q000473:pathology* / Q000503:physiopathology; D000437:Alcoholism / Q000473:pathology* / Q000503:physiopathology; D000818:Animals; D002492:Central Nervous System Depressants / Q000009:adverse effects; D002908:Chronic Disease; D049229:Dendritic Spines / Q000187:drug effects* / Q000473:pathology*; D000431:Ethanol / Q000009:adverse effects; D018698:Glutamic Acid / Q000378:metabolism; D019044:Image Cytometry; D007150:Immunohistochemistry; D008297:Male; D018613:Microscopy, Confocal; D009714:Nucleus Accumbens / Q000187:drug effects* / Q000473:pathology* / Q000503:physiopathology; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000378:metabolism; D012201:Reward; D019966:Substance-Related Disorders / Q000473:pathology / Q000503:physiopathology; D013569:Synapses / Q000187:drug effects / Q000473:pathology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
chemical_list: D002492:Central Nervous System Depressants; C409466:NR1 NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D000431:Ethanol; D018698:Glutamic Acid