Nalbuphine is effective in decreasing the rewarding effect induced by morphine in rats.
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.
Tao
Pao-Luh
PL
Department of Pharmacology, National Defense Medical Center, 161, Min-Chuan East Road, Sec. 6, Taipei 114, Taiwan, ROC.
Liang
Kai-Wen
KW
Sung
Wen-Yi
WY
Wu
Yung-Tsun
YT
Huang
Eagle Yi-Kung
EY
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002851:Chromatography, High Pressure Liquid; D003213:Conditioning, Psychological; D004361:Drug Tolerance; D006719:Homovanillic Acid / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000493:pharmacokinetics; D009266:Nalbuphine / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D009294:Narcotics / Q000008:administration & dosage / Q000493:pharmacokinetics; D009714:Nucleus Accumbens / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012201:Reward
D009292:Narcotic Antagonists; D009294:Narcotics; D015102:3,4-Dihydroxyphenylacetic Acid; D009020:Morphine; D009266:Nalbuphine; D006719:Homovanillic Acid