The ability of NK1R antagonism to suppress stress-induced reinstatement of alcohol seeking without affecting baseline self-administration or cue-induced reinstatement is reminiscent of compounds that target the CRF1R (Koob and Zorrilla, 2010; Shalev et al., 2010). These compounds also control escalated alcohol consumption that results from neuroadaptations induced by a history of alcohol dependence, or in models where escalation has resulted from genetic selection for alcohol preference (Heilig and Koob, 2007). In other words, these compounds are primarily effective under conditions where the activity of stress-responsive systems has been persistently up-regulated. A hypothesis that remains to be addressed is whether NK1R antagonists, while leaving basal alcohol intake unaffected, might be able to suppress escalated alcohol consumption. It will also be important to assess whether NK1R antagonism will be able to influence stress-induced relapse to drug seeking and escalated (as opposed to basal) self-administration of others drug classes, including opioids and cocaine.
