In this context, it seems particularly important to point out that (i) pCREB appears to have an important role in the addiction process57, 58 and (ii) the PKA/pCREB signal has been implicated in the molecular changes that underlie alcohol drinking and alcoholism.59, 60, 61 However, although our data document increased TLR4 expression in the VTA from alcohol-drinking P rats, the ligands responsible for its activation and PKA/pCREB/TH upregulation are still unclear. Here, TLR4 is linked to alcohol drinking.