In a recent study it was also shown that intracranial N/OFQ administration abolished somatic withdrawal signs during acute withdrawal, and significantly attenuates anxiety-like behavior during protracted abstinence (Economidou et al., 2011). These data suggest that, in addition to their potential as medications for excessive alcohol consumption and relapse, agonists for NOPRs may also have utility to treat alcohol withdrawal. Wistar rats tested for alcohol self-administration one week following withdrawal from chronic dependence were more sensitive both to the alcohol intake-reducing and to the anxiolytic-like actions of N/OFQ than non-dependent control rats (Aujla et al., 2012; Economidou et al., 2011; Martin-Fardon et al., 2010). However, three weeks into abstinence, ICV N/OFQ administration resulted in anxiogenic-like effects in rats with a history of alcohol dependence, while it continued to exert anxiolytic-like actions in controls.
