Abstract
Alcohol increases inhibitory neurotransmission, an effect mediated through GABA receptors. With chronic alcohol exposure, the inhibitory effects diminish. Glutamic acid decarboxylase (GAD) catalyzes glutamate in the synthesis of GABA. We sought to determine the amount of GAD65/67 mRNA in anterior cingulate cortex (BA24) and orbital prefrontal cortex (BA45) of medication-free alcoholics and nonpsychiatric controls postmortem.Studies were performed in 16 pairs of nonpsychiatric controls and alcoholics, matched for age, sex and PMI. DSM-IV diagnosis of alcohol use disorder (AUD) was made by the SCID I in a psychological autopsy. Frozen blocks of BA24 or BA45 were sectioned (10 µm) for in situ hybridization of 35S-labelled riboprobe for GAD65/67 mRNA and autoradiograms were analyzed by quantitative densitometry. Three isodensity bands of labeling were evident, with different relative amounts of GAD65 and GAD67 (outer and inner, predominantly GAD65, intermediate predominantly GAD67), and the isodensity bands were analyzed separately.GAD65/67 mRNA levels were not different between alcoholics and controls in the gray matter of BA24 (p = 0.53) or BA45 (p = 0.84) or in any of the three isodensity bands in which the GAD65/67 mRNA was distributed. GAD65/67 mRNA in white matter underlying either region was also not different in alcoholics (p > 0.05). GAD65/67 mRNA levels did not correlate with age, sex or duration of alcoholism in either BA24 or BA45.Effects on inhibitory neurotransmission in alcoholics do not appear to be associated with change in the levels of GAD65 or GAD67 mRNA.
Highlights
Alcohol consumption produces dose-dependent inhibition of the central nervous system (CNS) [1]
GAD65/67 mRNA expression was evident throughout the gray matter of BA24 and BA45 in both controls and alcohol use disorder (AUD) cases (Figure 1)
AUD cases have a comparable amount of GAD65/67 mRNA as controls in the gray matter of BA24 (F1,14= 0.421, p = 0.53) and BA45 (F1,13 = 0.045, p = 0.84)
Summary
Alcohol consumption produces dose-dependent inhibition of the central nervous system (CNS) [1]. Alcohol has effects on lipid bilayers and affects multiple neurotransmitters in multiple brain regions (see [2,3] for review). The CNS inhibition brought about by alcohol exposure is attributed to inhibition of excitatory glutamatergic neurotransmission [4,5] and by ethanol acting as an indirect gamma-aminobutyric acid (GABA) agonist [6]. GABA is the main inhibitory neurotransmitter in the brain, and ethanol acts through actions on GABAA receptors (e.g., [7,8], decreasing neuronal excitability (see [9] for review). There is neuronal adaptation and the inhibitory effects are reduced [5]
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 callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
