Loss of dopamine D2 receptors induces atrophy in the temporal and parietal cortices and the caudal thalamus of ethanol-consuming mice.
BACKGROUND
The need of an animal model of alcoholism becomes apparent when we consider the genetic diversity of the human populations, an example being dopamine D2 receptor (DRD2) expression levels. Research suggests that low DRD2 availability is associated with alcohol abuse, while higher DRD2 levels may be protective against alcoholism. This study aims to establish whether (i) the ethanol-consuming mouse is a suitable model of alcohol-induced brain atrophy and (ii) DRD2 protect the brain against alcohol toxicity.


METHODS
Adult Drd2+/+ and Drd2-/- mice drank either water or 20% ethanol solution for 6 months. At the end of the treatment period, the mice underwent magnetic resonance (MR) imaging under anesthesia. MR images were registered to a common space, and regions of interest were manually segmented.


RESULTS
We found that chronic ethanol intake induced a decrease in the volume of the temporal and parietal cortices as well as the caudal thalamus in Drd2-/- mice.


CONCLUSIONS
The result suggests that (i) normal DRD2 expression has a protective role against alcohol-induced brain atrophy and (ii) in the absence of Drd2 expression, prolonged ethanol intake reproduces a distinct feature of human brain pathology in alcoholism, the atrophy of the temporal and parietal cortices.
Laboratory of Neuroimaging, National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, Maryland, USA.
Foteini
F
Delis
Helene
H
Benveniste
Michalis
M
Xenos
David
D
Grandy
Gene-Jack
GJ
Wang
Nora D
ND
Volkow
Panayotis K
PK
Thanos
D000437:Alcoholism / Q000473:pathology; D000818:Animals; D001284:Atrophy / Q000139:chemically induced / Q000378:metabolism; D002492:Central Nervous System Depressants / Q000633:toxicity*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000473:pathology; D000431:Ethanol / Q000633:toxicity*; D008279:Magnetic Resonance Imaging; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009929:Organ Size / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D013788:Thalamus / Q000187:drug effects* / Q000473:pathology
D002492:Central Nervous System Depressants; D017448:Receptors, Dopamine D2; D000431:Ethanol