Animals were trained to self-administer ethanol and dependence was induced using an intermittent ethanol vapor exposure paradigm. Following the induction of dependence, escalation of self-administration was evaluated during acute withdrawal. An initial cohort of animals demonstrated that, following dependence induction, escalation of self-administration occurs according to a typical learning curve. In the first experiment, once animals had learned to self-administer ethanol, ICV FN-439 was chronically infused during the dependence induction period and subsequent post-dependence self-administration sessions. In the second experiment, following the dependence induction period, FN-439 was infused ICV prior to and immediately after self-administration sessions. To protect against Type I error in the second experiment (i.e., rejecting the null hypothesis when it is actually true) that could be attributable to non-specific effects of FN-439, the specificity of FN-439 for learning-related processes was confirmed by evaluating FN-439 effects in animals that displayed escalated responding. Further, to ensure that FN-439 did not permanently impair the ability of animals to learn, those animals that had originally been treated with FN-439 were subsequently infused with aCSF and the presence or absence of escalated responding was evaluated.
