Abstract
The central amygdala (CeA) has a role for mediating fear and anxiety responses. It is also involved in emotional imbalance caused by alcohol abuse and dependence and in regulating relapse to alcohol abuse. Growing evidences suggest that excitatory glutamatergic and inhibitory γ-aminobutyric acid-ergic (GABAergic) transmissions in the CeA are affected by chronic alcohol exposure. Human post-mortem CeA samples from male alcoholics (n = 9) and matched controls (n = 9) were assayed for the expression level of ionotropic glutamate and GABA-A receptors subunit mRNAs using quantitative real-time reverse transcription-PCR (RT-qPCR). Our data revealed that out of the 16 ionotropic glutamate receptor subunits, mRNAs encoding two AMPA [2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid] receptor subunits GluA1 and GluA4; one kainate receptor subunit GluK2; one NMDA (N-methyl-D-aspartate) receptor subunit GluN2D and one delta receptor subunit GluD2 were significantly decreased in the CeA of alcoholics. In contrast, of the 19 GABA-A receptor subunits, only the mRNA encoding the α2 subunit was significantly down-regulated in the CeA of the alcoholics as compared with control subjects. Our findings imply that the down-regulation of specific ionotropic glutamate and GABA-A receptor subunits in the CeA of alcoholics may represent one of the molecular substrates underlying the new balance between excitatory and inhibitory neurotransmission in alcohol dependence.
Highlights
Alcoholism is a chronic relapsing brain disorder characterized by compulsive alcohol intake, progressive alcohol tolerance, dependence and behavioral impairments (Koob, 2013)
The mRNA expression of 16 ionotropic glutamate receptor subunits (AMPA subunits: GluA1-4; kainate subunits: GluK1-5; NMDA subunits: GluN1, 2A, 2B, 2C, 2D, 3A and 3B; glutamate receptor delta: GluD1 and 2) and 19 GABA-A receptor subunits (α1-6, β1-3, γ1-3, δ, ε, θ, π, ρ1-3) was quantified by RT-qPCR in the central amygdala (CeA) samples collected from nine control subjects and nine alcoholics
Brain pH, postmortem interval (PMI), smoking history, RNA Quality Indicator (RQI) or presence/absence of alcohol/benzodiazepines in the blood at death did not affect the significance between the two groups
Summary
Alcoholism is a chronic relapsing brain disorder characterized by compulsive alcohol intake, progressive alcohol tolerance, dependence and behavioral impairments (Koob, 2013). The CeA is the major output station of the amygdala and contains mostly GABAergic projection neurons. It receives multiple afferent inputs from, e.g., the cortex and thalamus as well as glutamatergic input from the basolateral amygdala (BLA). The modulation of the dynamic balance between excitatory glutamatergic and inhibitory GABAergic neurotransmission in the CeA has been correlated with behavioral changes during chronic alcohol exposure and withdrawal (Kumar et al, 2009; McCool et al, 2010). Bilateral CeA microinjection of a GABA-A receptor antagonist decreases alcohol self-administration (Hyytia and Koob, 1995), whereas CeA injection of ionotropic glutamate receptor antagonist inhibits alcohol-induced reward behavior in animals (Zhu et al, 2007)
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