TOLERANCE AND CROSS-TOLERANCE TO THE ACCURACY-DECREASING AND RATE-DECREASING EFFECTS OF MU-OPIOIDS IN RATS RESPONDING UNDER A FIXED-CONSECUTIVE-NUMBER SCHEDULE

The purpose of the present investigation was to examine the developmen t of tolerance to the effects of morphine and other mu opioids in rats responding under a fixed-consecutive-number (FCN) schedule of food pr esentation. To this end, five rats were trained under an FCN schedule and subsequently tested with a variety of mu opioids both before and d uring chronic exposure to a 0.4 mg/ml morphine drinking solution. Morp hine, fentanyl, buprenorphine, butorphanol and nalbuphine produced dos e-dependent decreases in both accuracy and response rate when tested p rior to the chronic regimen. In most instances, doses of these drugs t hat decreased accuracy also decreased response rate. During chronic tr eatment, tolerance developed to the effects of morphine and cross-tole rance was conferred to the effects of fentanyl, buprenorphine and buto rphanol. A greater degree of tolerance was conferred to the effects of butorphanol than to the other opioids examined, and the degree of tol erance conferred to butorphanol's rate-decreasing effects was greater than the degree of tolerance conferred to its accuracy-decreasing effe cts. Doses of naloxone that had no effect prior to morphine treatment produced large decreases in accuracy and response rate when tested dur ing the chronic regimen. In contrast to the other opioids examined, th e potency of nalbuphine was not altered by chronic morphine administra tion. These data emphasize the importance of both pharmacological and procedural variables in the development of tolerance and cross toleran ce to the behavioral effects of opioids. (C) 1997 Elsevier Science Ire land Ltd.