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Enhanced motivation to alcohol in transgenic mice expressing human α‐synuclein
Author(s) -
Rotermund Carola,
Reolon Gustavo K.,
Leixner Sarah,
Boden Cindy,
Bilbao Ainhoa,
Kahle Philipp J.
Publication year - 2017
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.14151
Subject(s) - transgene , nucleus accumbens , genetically modified mouse , amygdala , addiction , microinjection , alpha synuclein , ethanol , biology , gene , endocrinology , neuroscience , medicine , genetics , parkinson's disease , disease , central nervous system , biochemistry
α‐Synuclein (α SYN ) is the neuropathological hallmark protein of Parkinson's disease ( PD ) and related neurodegenerative disorders. Moreover, the gene encoding α 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 α SYN expression in blood. To investigate the effect of α 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]α 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 α SYN transgenic mice, while in wild‐type mice no effect was visible. However, at the same time, levels of cF os 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.