Functional impairment of the orbital and medial prefrontal cortex underlies 
deficits in executive control that characterize addictive disorders, including 
alcohol addiction. Previous studies indicate that alcohol alters glutamate 
neurotransmission and one substrate of these effects may be through the 
reconfiguration of the subunits constituting ionotropic glutamate receptor 
(iGluR) complexes. Glutamatergic transmission is integral to cortico-cortical 
and cortico-subcortical communication and alcohol-induced changes in the 
abundance of the receptor subunits and/or their splice variants may result in 
critical functional impairments of prefrontal cortex in alcohol dependence. To 
this end, the effects of chronic ethanol self-administration on glutamate 
receptor ionotropic AMPA (GRIA) subunit variant and kainate (GRIK) subunit mRNA 
expression were studied in the orbitofrontal cortex (OFC), dorsolateral 
prefrontal cortex (DLPFC), and anterior cingulate cortex (ACC) of male 
cynomolgus monkeys. In DLPFC, total AMPA splice variant expression and total 
kainate receptor subunit expression were significantly decreased in alcohol 
drinking monkeys. Expression levels of GRIA3 flip and flop and GRIA4 flop mRNAs 
in this region were positively correlated with daily ethanol intake and blood 
ethanol concentrations (BEC) averaged over the 6 months prior to necropsy. In 
OFC, AMPA subunit splice variant expression was reduced in the alcohol treated 
group. GRIA2 flop mRNA levels in this region were positively correlated with 
daily ethanol intake and BEC averaged over the 6 months prior to necropsy. 
Results from these studies provide further evidence of transcriptional 
regulation of iGluR subunits in the primate brain following chronic alcohol 
self-administration. Additional studies examining the cellular localization of 
such effects in the framework of primate prefrontal cortical circuitry are 
warranted.