Changes in sensitivity to the rate-decreasing effects of opioids in pigeons treated acutely or chronically with nalbuphine.
This study examined whether tolerance or dependence develops to the effects of the low-efficacy µ opioid agonist nalbuphine on schedule-controlled responding. In untreated pigeons responding under a fixed ratio (FR)-20 schedule of food presentation, nalbuphine, naltrexone, morphine, fentanyl, etonitazene and enadoline decreased response rates. Naltrexone (0.1-10.0mg/kg) did not antagonize the rate-decreasing effects of nalbuphine. In a separate group of pigeons, chronic nalbuphine treatment (1.0-56.0mg/kg/day) did not alter the sensitivity of pigeons to the rate-decreasing effects of nalbuphine or naltrexone. In pigeons treated with 56.0mg/kg/day of nalbuphine, dose-effect curves for µ and kappa agonists were shifted 3- to 10-fold to the right of dose-effect curves determined prior to chronic treatment. The rate-decreasing effects of nalbuphine did not appear to be mediated by opioid receptors, as evidenced by the inability of naltrexone to antagonize nalbuphine and the lack of tolerance development. Although chronic nalbuphine altered the sensitivity to the rate-decreasing effects of µ and kappa agonists, there was no change in sensitivity to naltrexone. To the extent that increased sensitivity to antagonists is indicative of dependence, these data suggest that opioid dependence does not develop to nalbuphine.
Department of Pharmacology, Louisiana State University Medical Center, 1100 Florida Avenue, New Orleans, LA 70119, USA.
L.R.
LR
Gerak
C.P.
CP
France