The PAG plays important roles in the processing of pain, fear and anxiety (reviewed in Behbehani, 1995). Anxiety and fear are commonly associated with alcohol withdrawal (Pandey et al., 2015, Koob, 2013). Animals exposed to ethanol during adolescence were, as adults, more anxious and drank more than the animals not previously exposed to ethanol (Pandey et al., 2015). Furthermore, the PAG receives significant serotonergic innervation from the DRN involved in fight-or-flight behavioral responses (Johnson et al., 2004). Li et al. (2013) reported that acute ethanol produced a robust enhancement of glutamatergic synaptic transmission in the PAG. GABAA and μ opioid receptors (Silva and Nobre, 2014) and glutamate receptors (Ezequiel Leite and Nobre, 2012; Long et al., 2007) within the PAG are affected in ethanol withdrawal. Microinjection of NMDA or AMPA antagonists into the PAG reduced ethanol intake during withdrawal (Ezequiel Leite and Nobre, 2012). In addition, there may be an association between chronic pain and alcohol dependence, suggesting overlapping neural mechanisms (Apkarian et al., 2013). But thus far, the global effects of ethanol on changes in gene expression within the PAG have not been studied.
