“…In cell culture and animal studies, chronic exposure to naltrexone produces upregulation of MOR protein levels in the ventral tegmental area and nucleus accumbens, regions important in nicotine addiction (Tempel et al 1985). Previous laboratory investigations showing smoking reduction following naltrexone treatment have tested acute, single-dose administration, which would not be expected to produce upregulation in MOR (Epstein and King 2004;Hutchison et al 1999;King and Meyer 2000;Rukstalis et al 2005). However, other studies have documented reductions in smoking with short-term or long-term naltrexone treatment (Covey et al 1999;Wewers et al 1998) and with 100 mg naltrexone therapy (O'Malley et al 2006), suggesting that tolerance to naltrexone may not be an adequate explanation for the lack of medication effects in the present study.…”