Abstract
Chronic consumption of alcohol by humans has been shown to lead to impairment of executive and cognitive functions. Here, we have studied the mRNA expression of ion channel receptors for glutamate and GABA in the dorsal striatum of post-mortem brains from alcoholics (n = 29) and normal controls (n = 29), with the focus on the caudate nucleus that is associated with the frontal cortex executive functions and automatic thinking and on the putamen area that is linked to motor cortices and automatic movements. The results obtained by qPCR assay revealed significant changes in the expression of specific excitatory ionotropic glutamate and inhibitory GABA-A receptor subunit genes in the caudate but not the putamen. Thus, in the caudate we found reduced levels of mRNAs encoding the GluN2A glutamate receptor and the δ, ε, and ρ2 GABA-A receptor subunits, and increased levels of the mRNAs encoding GluD1, GluD2, and GABA-A γ1 subunits in the alcoholics as compared to controls. Interestingly in the controls, 11 glutamate and 5 GABA-A receptor genes were more prominently expressed in the caudate than the putamen (fold-increase varied from 1.24 to 2.91). Differences in gene expression patterns between the striatal regions may underlie differences in associated behavioral outputs. Our results suggest an altered balance between caudate-mediated voluntarily controlled and automatic behaviors in alcoholics, including diminished executive control on goal-directed alcohol-seeking behavior.
Highlights
In the mammalian brain the areas identified as caudate and putamen are parts of the striatum and participate in neuronal circuits directing complex behavior (Postuma and Dagher, 2006; Grahn et al, 2008; Depoy et al, 2013)
We examined whether chronic alcohol consumption in humans changes the balance between excitation and inhibition in the post-mortem caudate and putamen by analyzing the mRNA expression levels of the glutamate- and Glutamate and γ-aminobutyric acid (GABA)-activated receptor subunits
UNALTERED mRNAs EXPRESSION OF GLUTAMATE AND GABA-A RECEPTOR SUBUNITS IN THE PUTAMEN OF ALCOHOLICS We examined the mRNA expression of the glutamate and GABA-A receptor subunits in the putamen from alcoholics and individuals without alcohol dependence
Summary
In the mammalian brain the areas identified as caudate and putamen are parts of the striatum and participate in neuronal circuits directing complex behavior (Postuma and Dagher, 2006; Grahn et al, 2008; Depoy et al, 2013). Glutamate and γ-aminobutyric acid (GABA) are the main excitatory and inhibitory neurotransmitters, respectively, in the brain and normally maintain the proper level of excitation in neuronal circuits (Smart and Paoletti, 2012) Both glutamate- and GABA-activated ionotropic receptors are multi-subunit channels (Smart and Paoletti, 2012). We examined whether chronic alcohol consumption in humans changes the balance between excitation and inhibition in the post-mortem caudate and putamen by analyzing the mRNA expression levels of the glutamate- and GABA-activated receptor subunits. The results show significant changes in the expression of specific excitatory ionotropic glutamate receptor genes and specific inhibitory GABA-A receptor genes in the caudate but not the putamen of the striatum, indicating that alcoholism-related alterations in the expression of the main excitatory and inhibitory receptor subunits are not similar in adjacent brain regions
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
