Nalbuphine is effective in decreasing the rewarding effect induced by morphine in rats

Drug Alcohol Depend. 2006 Sep 15;84(2):175-81. doi: 10.1016/j.drugalcdep.2006.01.013. Epub 2006 Mar 6.


Nalbuphine, a kappa-opioid agonist and mu-opioid partial agonist, has been widely used as an analgesic or an adjuvant with morphine in clinics. In rats, it attenuates tolerance and physical dependence caused by morphine, when co-administered. In this study, we investigated the effect of nalbuphine on morphine reward. Using the conditioned place preference (CPP) paradigm in rats, we demonstrated that co-administration of nalbuphine (1mg/kg, i.p.) with morphine (5mg/kg, i.p.) during conditioning could completely block the CPP induced by morphine. However, in experiments examining locomotor activity in rats, nalbuphine showed no effect on the development of behavioral sensitization induced by reported morphine administration. In microdialysis experiments, morphine induced a significant increase in the dopamine metabolites 3,4-dihydroxyphenylacetic acid and homovanillic acid in the shell region of the nucleus accumbens. Co-administration of nalbuphine blocked the increase in dopamine metabolites induced by morphine. These results may be due to the attenuating effect of nalbuphine on the dopaminergic activity of mesolimbic pathways. All of these results suggest nalbuphine could have a great potential as a pharmacotherapy for opiate abuse.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / metabolism
  • Animals
  • Behavior, Animal / drug effects*
  • Chromatography, High Pressure Liquid
  • Conditioning, Psychological
  • Drug Tolerance
  • Homovanillic Acid / metabolism
  • Locomotion / drug effects
  • Male
  • Morphine / administration & dosage
  • Morphine / antagonists & inhibitors*
  • Morphine / pharmacokinetics
  • Nalbuphine / administration & dosage
  • Nalbuphine / pharmacokinetics
  • Nalbuphine / pharmacology*
  • Narcotic Antagonists / administration & dosage
  • Narcotic Antagonists / pharmacokinetics
  • Narcotic Antagonists / pharmacology*
  • Narcotics / administration & dosage
  • Narcotics / pharmacokinetics
  • Nucleus Accumbens / drug effects
  • Nucleus Accumbens / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Reward*


  • Narcotic Antagonists
  • Narcotics
  • 3,4-Dihydroxyphenylacetic Acid
  • Morphine
  • Nalbuphine
  • Homovanillic Acid