UC San Diego

Previous studies have shown that ethanol dependence induced by repeating cycles of chronic intermittent ethanol vapor exposure (CIE) followed by protracted abstinence (CIE-PA) produces significant alterations in gliogenesis in the rodent medial prefrontal cortex (mPFC). Specifically, CIE-PA has been shown in previous studies to significantly dysregulate the process of myelinating oligodendrocytes in the mPFC by creating an unprecedented increase in premyelinating oligodendroglial progenitor cell (OPC) proliferation and survival, which has been associated with persistent elevated drinking behaviors during abstinence. In the current thesis, 63 male adult Wistar rats were subjected to seven weeks of CIE and were examined following 1 day(d), 7d, 21d, or 42d of abstinence. Neuroimaging, capable of detecting alterations to the myelination integrity of the mPFC in vivo, was performed in CIE-PA and age-matched non-vapor control rats, in parallel with conventional immunohistochemical methods to better characterize the physiological changes underlying any neuroimaging metric changes. This neuroimaging technique, called diffusion tensor imaging (DTI), successfully detected abstinence-related changes in the mPFC, specifically that CIE-PA produced transient increases in fractional anisotropy (FA) at the 7d abstinence time point compared to controls and other time points. Interestingly, this increase in FA, was associated temporally with increases in myelin basic protein (MBP), myelin oligodendrocyte glycoprotein (MOG), 2’3’-cyclic-nucleotide 3’-phosphodiesterase (CNPase) that we observed also occurred at the 7d PA time point. Therefore, this study concluded that DTI is capable of detecting myelination related changes in the mPFC that result from CIE-PA.