Opioids are proposed to play a role in the control of food intake since administration of opioids increase food intake while administration of opioid antagonists decrease food intake. In these experiments responses to a new opioid antagonist, nalmefene, were measured in Zucker obese and lean rats. In obese male rats 1 mg/kg nalmefene decreased the size of the first meal after a 10-hr fast and decreased 14-hr food intake, indicating nalmefene is relatively long-acting. Administration of 1 mg/kg nalmefene daily for 7 days decreased average meal size and daily food intake and increased meal frequency; feeding responses on day 7 were similar to those on day 1, suggesting a lack of development of tolerance. Food and water intake and weight gain during a 3-week treatment period were decreased more in lean rats by low doses of nalmefene (up to 0.25 mg/kg) and more in obese rats by higher doses of nalmefene (0.50 mg/kg). These responses to a new opioid antagonist further support a possible role for opioids in the control of food intake.
