Many of the genes, which differed between the alcohol-naive P vs. NP rats and changed in the opposite direction with alcohol drinking (Table 6), promoted pro-inflammatory responses and induced programmed cell death (Table 7). The innate differences in the lower expression of genes involved in the immune and inflammatory responses in the VTA of the P compared to the NP line (e.g., C3, Serpinb9, B2m, C1qa, Fcer1g, Itgb2, Pycard, Aif1; Tables 6 and 7) could be factors contributing to the vulnerability of the P line to high alcohol drinking behavior. Recent findings (Crews et al., 2013) are compatible with the present results of increased brain neuroimmune activation in alcohol dependence. These results (Tables 6 and 7) are in agreement with the overall analysis of the data indicating a negative impact of this excessive binge-like drinking protocol by P rats (Table 8). On the other hand, the complement system has been implicated in synaptic plasticity (Stephan et al., 2012), and some of the changes observed in the immune process and inflammatory response may result in positive alterations in synaptic function. The
