Murley, Jordan; Stockard, Alyssa; Payne, Andrew; Steffensen, Scott (Brigham Young University)
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences; Psychology)
Brain-derived neurotrophic factor (BDNF) is implicated in varied physiological processes. Its main receptor in the central nervous system is tyrosine receptor kinase B (TrkB), and the main ligand for TrkB in the central nervous system is BDNF. It has been shown previously that activating TrkB can cause a downregulation of the chloride-exporting potassium chloride cotransporter 2 (KCC2), presumably resulting in a decreased chloride gradient. It is hypothesized that this down-regulation, caused by an increase in BDNF levels, creates hyperexcitable GABA neurons in the ventral tegmental area (VTA) due to a reduced efficacy of inhibitory currents. Here we investigate this mechanism of adaptation in the context of chronic alcohol exposure. We demonstrate that BDNF levels are elevated in the VTA during withdrawal from chronic alcohol exposure. We also observe that blocking TrkB activity decreases alcohol seeking behavior. Further, we investigate the expression patterns of KCC2 in connection with chronic alcohol administration. Additional work is underway to validate this mechanism and further elucidate its putative role in alcohol dependence.