Clarke, Eliza; Williams, Stephanie; Payne, Andrew; Obray, J Daniel; Yorgason, Jordan; Steffensen, Scott (Brigham Young University)
Faculty Advisor: Steffensen, Scott (Family, Home, and Social Sciences; Psychology)
Dopamine (DA) transmission is a key player in the rewarding aspects of ethanol as well as ethanol dependence. The current dogma is that DA transmission is increased during ethanol exposure via the inhibition of ventral tegmental area (VTA) GABA neurons and that excitation of VTA GABA neurons during withdrawal results in decreased DA transmission. Microglia, the major neuroimmune effector in the brain, may be a key mediator in this process by releasing cytokines following activation. It is also thought that BDNF may mediate this effect. We evaluated the effect of ethanol on cytokine concentrations in the VTA and nucleus accumbens (NAc), and found that low dose ethanol (1.0 g/kg) decreased interleukin (IL)-10 levels, but high dose ethanol (4.0 g/kg) increased IL-10 levels. We also used standard cell-attached mode electrophysiological techniques to evaluate the effects of select cytokines and BDNF on VTA neuron firing rate in vitro. We found no change in firing rate in response to IL-6 and BDNF, but an increase in firing rate in VTA DA neurons in response to IL-10. Consistent with the changes in firing rate, optically-evoked IPSCs were also found to be decreased in response to IL-10. Ex vivo voltammetry and in vivo microdialysis were done to determine whether IL-10 can directly result in an increase in DA release. Although ex vivo voltammetry showed no change in DA release, IL-10 increased DA release in vivo. These findings suggest that the rewarding and/or addictive effects of ethanol may be mediated by cytokines, specifically the anti-inflammatory cytokine IL-10.