Disruption of chemokine signaling also impacts alcohol behaviors. Genetic deletion of CCR2, CCL2 (in females), or CCL3 reduces voluntary ethanol consumption and conditioned place preference (CPP) to ethanol in mice (Blednov et al., 2005). Silencing Ccl2 in the CeA or VTA of rats decreases ethanol consumption (June et al., 2015). In contrast, directly infusing CCL2 into cerebral ventricles of rats led to increased operant ethanol self-administration (Valenta and Gonzales, 2016). Midkine (MDK), a cytokine and neurotrophic factor which regulates CCL2 expression, may function to limit ethanol consumption, as MDK KO mice and mice expressing Mdk shRNA in the VTA demonstrate increased drinking (Chen et al., 2017a).
