The novel kappa-opioid receptor agonist TRK-820 suppresses the rewarding and locomotor-enhancing effects of morphine in mice.
The effects of the novel kappa-opioid receptor agonist TRK-820 on the rewarding and locomotor-enhancing effects of morphine were investigated in mice. Morphine (1-5 mg/kg, s.c.) caused a dose-related preference for the drug-associated place. In contrast, TRK-820 (0.003-0.03 mg/kg, s.c.) did not produce a significant preference for either compartment of the test box. In combination studies, co-injection of TRK-820 (0.01 and 0.03 mg/kg, s.c.) with morphine significantly suppressed the morphine (5 mg/kg, s.c.)-induced place preference, and this effect of TRK-820 was antagonized by pretreatment with nor-BN1 (3 mg/kg, s.c.), a selective kappa-opioid receptor antagonist. TRK-820 also suppressed morphine-induced hyperlocomotion, and this suppression was also blocked by nor-BNI. These results suggest that TRK-820 suppresses the rewarding and locomotor-enhancing effects of morphine through the activation of kappa-opioid receptors. Thus, we propose that TRK-820 may be useful for controlling pain while reducing undesirable side-effects.
Tsuji
M
M
Department of Pharmacology, Tokyo Medical University, Japan.
Takeda
H
H
Matsumiya
T
T
Nagase
H
H
Narita
M
M
Suzuki
T
T
D000818:Animals; D004305:Dose-Response Relationship, Drug; D008297:Male; D051379:Mice; D009019:Morphinans / Q000494:pharmacology*; D009020:Morphine / Q000494:pharmacology*; D009043:Motor Activity / Q000187:drug effects*; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D017473:Receptors, Opioid, kappa / Q000819:agonists*; D012201:Reward; D013141:Spiro Compounds / Q000494:pharmacology*
D009019:Morphinans; D009294:Narcotics; D017473:Receptors, Opioid, kappa; D013141:Spiro Compounds; C111212:TRK 820; C051844:norbinaltorphimine; D009271:Naltrexone; D009020:Morphine