Interactions of clonidine and naloxone on schedule-controlled behavior in opioid-naive mice

Schedule-controlled responding was maintained under a fixed-ratio schedule in mice. Administered alone, clonidine, morphine and naloxone produced dose-related decreases in rates of responding, with clonidine about 100 times more potent than morphine which was about ten times more potent than naloxone. Decreases in response rates produced by high doses of naloxone were antagonized by clonidine (0.003-0.1 mg/kg) in a dose-dependent manner; however, decreases in response rates produced by clonidine (0.3 mg/kg) were not antagonized by naloxone (1.0-100 mg/kg). Effects of high doses of naloxone (100 mg/kg) were not antagonized by morphine (1.0-100 mg/kg) whereas effects of morphine (17.0 mg/kg) were antagonized by naloxone (0.01-1.0 mg/kg). Thus, clonidine can reverse behavior-disrupting effects of naloxone in non-dependent subjects, indicating that at least some of the interactions of these two drugs are not specific to the opioid-dependent state.