Development of enhanced sensitivity to naloxone

The effects of naloxone were examined over a period of three and a half years in squirrel monkeys responding under a mult FR, FI schedule of food presentation. During the initial observation of naloxone's effects, monkeys were drug naive. At that time, doses of naloxone up to 3.0 mg/kg had very little effect on rates of responding under the multiple schedule. The effects of naloxone were then examined in combination with meperidine. Doses of naloxone between 0.3 and 3.0 mg/kg produced a dose-dependent antagonism of meperidine's effects. Monkeys were then exposed to ketocyclazocine and phencyclidine, alone and in combination with naloxone. When the naloxone dose-effect curve was redetermined subsequently, it had shifted to the left. Monkeys were then exposed to buprenorphine and diprenorphine, alone and in combination with naloxone. Redetermination of the naloxone dose-effect curve following this exposure revealed a further shift to the left. The effects of naloxone were then reexamined in combination with meperidine, and it was found that the leftward shift in the naloxone dose-effect curve was not accompanied by a decrease in the doses of naloxone which would reverse the effects of meperidine. Naloxone's effects were then examined in combination with either acute or chronic diazepam. The naloxone dose-effect curve determined during the chronic diazepam regimen was shifted to the right of that obtained prior to chronic diazepam.