Protracted Abstinence from Chronic Ethanol Experience alters Plasticity Related Proteins and Excitability of Pyramidal Neurons in the Rodent Medial Prefrontal Cortex

The rodent medial prefrontal cortex (mPFC) is a brain region that is homologous to the human PFC, a brain region within the limbic system that has been implicated in executive functions and in alcohol relapse. Previous studies in rodents have demonstrated that inducing ethanol dependence through chronic intermittent ethanol vapor exposure paradigms followed by forced protracted abstinence increases drinking during abstinence, and causes significant alterations in neuronal excitability and white matter/cerebrovascular composition in the mPFC. However, no studies have investigated the cellular and molecular changes associated with the neuroplastic adaptations that occur within this brain region during protracted abstinence. To investigate this, 69 adult male Wistar rats underwent seven weeks of chronic intermittent ethanol exposure and were then subject to either 1 day, 7 days, 21 days, or 42 days of protracted abstinence. Afterwards these animals were immediately euthanized and tissue from mPFC of their brains was collected for analysis via Western blotting or for analysis via ex vivo electrophysiology. We found that chronic intermittent ethanol experience followed by 21 days of protracted abstinence produced a significant decrease in levels of phosphorylated calcium calmodulin kinase II (CaMKII) along with a decrease in the ratio of glutamatergic subunits GluN2A/2B of the NMDA receptor. This reduction in CaMKII activity and the ratio of GluN2A/2B was associated with enhanced excitability of layer 2/3 pyramidal neurons in the mPFC. Together, the present results indicate adaptive biochemical changes in excitatory neurotransmitter systems in the mPFC and highlights the importance of exploring neuroplasticity changes that predict enhanced propensity to relapse alcohol-seeking behaviors