A new buprenorphine analogy, thenorphine, inhibits morphine-induced behavioral sensitization in mice.
OBJECTIVE
To investigate effects of thenorphine, a new compound of partial agonist of mu-opioid receptor, on the locomotor activity and the behavioral sensitization to morphine in mice.


METHODS
Locomotor activity was observed after administration of thenorphine or co-administration of thenorphine and morphine in mice. Mice were induced behavioral sensitization to morphine by intraperitoneal injection of 20 mg/kg morphine once daily for 7 d. Thenorphine was co-administrated with morphine to observe the effects of thenorphine on the development, transfer and expression of morphine-induced behavioral sensitization.


RESULTS
A single dose of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the locomotor activity in mice (P<0.05), repeated administrations of thenorphine, however, were not able to induce locomotor sensitization, but induced tolerance. Pretreatment with thenorphine 30 min prior to morphine effectively inhibited the psychomotor effect of morphine in mice (P<0.01). Co-administration of thenorphine (0.0625, 0.25, and 1.0 mg/kg) could dose-dependently inhibit the development, transfer, and expression of behavioral sensitization to morphine in mice (P<0.05 or P<0.01).


CONCLUSIONS
Thenorphine inhibited morphine-induced behavioral sensitization in mice, suggesting that thenorphine may be effective against the addiction of opioids.
Zhao
Wen-li
WL
Department of Neuropharmacology, National Institute on Drug Dependence, Peking University, Beijing, China.
Gong
Ze-hui
ZH
Liang
Jian-hui
JH
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002047:Buprenorphine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004361:Drug Tolerance; D005260:Female; D008297:Male; D051379:Mice; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000819:agonists
D017450:Receptors, Opioid, mu; C497654:thenorphine; D002047:Buprenorphine; D009020:Morphine