in Ser133–pCREB within specific neurocircuitry of the frontal, parietal, and piriform cortex in rats (82), suggesting the possibility that CREB-dependent events in these cortical structures may be involved in the development of alcohol dependence. Among the mechanisms responsible for reduced pCREB and downregulation of cAMP-dependent genes, chronic intermittent alcohol exposure has been shown to increase expression of the protein kinase inhibitor-α (PKI-α) in the PFC, nucleus accumbens, and AMG in Wistar rats (83). Given the wealth of data for the recruitment of the cAMP–PKA signaling pathways upon acute ethanol exposure, it has been proposed that the increased PKI-α expression may be part of the adaptation of the cAMP–PKA pathway induced by intermittent alcohol exposure.
