Evidence for a role for OXT in the regulation of withdrawal symptoms came from early seminal studies demonstrating that OXT administration decreased naloxone-precipitated morphine withdrawal symptoms in rats (Bicknell et al., 1988, Kovács and Van Ree, 1985). Oxytocin administration prior to alcohol exposure was also found to modulate the severity of alcohol withdrawal symptoms (e.g. picrotoxin-induced seizures) though these effects appear to be dose-dependent (Szabo et al., 1987). Additionally, central administration of OXT (icv.) was shown to block rapid tolerance to the effects of alcohol (Szabo et al., 1989). Interestingly, central administration was found to be more efficacious than peripheral administration, pointing to a centrally mediated mechanism (Szabo et al., 1989). Recent work by Manbeck and colleagues showed that OXT (0.06 −1.0mg/kg; i.p.) blocked withdrawal-induced elevations in somatic measures in nicotine-dependent rats (Manbeck et al., 2014). Further, Zanos et al. (2014) demonstrated that a single dose (6.4 mg/kg, ip.) of the OXT analogue carbetocin administered to morphine-dependent mice during withdrawal reduced levels of withdrawal-induced anxiety, depression and social anxiety behavior, suggesting a role for OXT in augmentation of withdrawal-related emotional dysregulation.
