Discrimination among morphine, saline and naltrexone in rhesus monkeys receiving morphine subchronically

Discriminative control was established among morphine, saline and naltrexone in rhesus monkeys receiving morphine every other day. Three hours prior to sessions subjects received saline or 3.2 mg/kg morphine; immediately prior to sessions they received saline or 0.01 mg/kg of naltrexone. There were dose-related generalizations to each training condition: morphine generalized to the morphine plus saline lever; small doses of naltrexone reversed effects of morphine and larger doses occasioned responding on the morphine plus naltrexone lever; in one monkey still larger doses occasioned responding on the saline plus saline lever. When saline was administered 3 h earlier, naltrexone had no effect in one subject and occasioned responding on the morphine plus naltrexone lever in a second subject. Nalbuphine substituted for morphine plus saline in one monkey and for morphine plus naltrexone in a second monkey; ketamine did not substitute for either training drug. That stimulus control was established between no drug and a combination of morphine and naltrexone suggests the latter condition did not represent the absence of morphine. In addition to demonstrating stimulus control for three conditions in rhesus monkeys, the current study suggests opioid antagonists might have novel discriminative stimulus effects at opioid receptors even under conditions where signs of withdrawal are not evident.