Enhanced motivation to alcohol in transgenic mice expressing human [alpha]-synuclein

[alpha]-Synuclein ([alpha]SYN) is the neuropathological hallmark protein of Parkinson's disease (PD) and related neurodegenerative disorders. Moreover, the gene encoding [alpha]SYN (SNCA) is a major genetic contributor to PD. Interestingly, independent genome-wide association studies also ident...

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Bibliographic Details
Published inJournal of neurochemistry Vol. 143; no. 3; p. 294
Main Authors Rotermund, Carola, Reolon, Gustavo K, Leixner, Sarah, Boden, Cindy, Bilbao, Ainhoa, Kahle, Philipp J
Format Journal Article
LanguageEnglish
Published New York Blackwell Publishing Ltd 01.11.2017
Subjects
Addictions
Alcoholic beverages
Alcoholism
Amygdala
Brain
Deprivation
Drug abuse
Drug self-administration
Environmental effects
Ethanol
Genome-wide association studies
Genomes
Genotypes
Human behavior
Mice
Motivation
Movement disorders
Neurodegenerative diseases
Nucleus accumbens
Operant conditioning
Parkinson's disease
Rodents
Synuclein
Transgenic animals
Transgenic mice
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Summary:[alpha]-Synuclein ([alpha]SYN) is the neuropathological hallmark protein of Parkinson's disease (PD) and related neurodegenerative disorders. Moreover, the gene encoding [alpha]SYN (SNCA) is a major genetic contributor to PD. Interestingly, independent genome-wide association studies also identified SNCA as the most important candidate gene for alcoholism. Furthermore, single-nucleotide-polymorphisms have been associated with alcohol-craving behavior and alcohol-craving patients showed augmented [alpha]SYN expression in blood. To investigate the effect of [alpha]SYN on the addictive properties of chronic alcohol use, we examined consumption, motivation, and seeking responses induced by environmental stimuli and relapse behavior in transgenic mice expressing the human mutant [A30P][alpha]SYN throughout the brain. The primary reinforcing effects of alcohol under operant self-administration conditions were increased, while consumption and the alcohol deprivation effect were not altered in the transgenic mice. The same mice were subjected to immunohistochemical measurements of immediate-early gene inductions in brain regions involved in addiction-related behaviors. Acute ethanol injection enhanced immunostaining for the phosphorylated form of cAMP response element binding protein in both amygdala and nucleus accumbens of [alpha]SYN transgenic mice, while in wild-type mice no effect was visible. However, at the same time, levels of cFos remain unchanged in both genotypes. These results provide experimental confirmation of SNCA as a candidate gene for alcoholism in addition to its known link to PD.
ISSN:0022-3042
1471-4159
DOI:10.1111/jnc.14151