Inhibitory effects of paeonol on morphine-induced locomotor sensitization and conditioned place preference in mice.
The inhibitory effects of paeonol, a major compound of Paeoniae radix, on the development of locomotor sensitization, conditioned place preference (CPP) and dopamine receptor supersensitivity induced by the repeated administration of morphine were investigated through behavioral experiments. A single administration of morphine produces hyperlocomotion. Repeated administration of morphine develops sensitization (reverse tolerance), a progressive enhancement of locomotion, which is used as a model for studying the drug-induced drug-seeking behaviors, and CPP, which is used as a model for studying drug reinforcement. Paeonol inhibited morphine-induced hyperlocomotion, sensitization and CPP. In addition, paeonol inhibited the development of postsynaptic dopamine receptors supersensitivity, which may be an underlying common mechanism that mediates the morphine-induced dopaminergic behaviors such as sensitization and CPP. Apomorphine (a dopamine agonist)-induced climbing behaviors also were inhibited by a single direct administration of paeonol. These results provide evidence that paeonol exerts anti-dopaminergic activity, and it is suggested that paeonol may be useful for the prevention and therapy of these adverse actions of morphine.
Eun
Jae Soon
JS
College of Pharmacy, Woosuk University, Samrye 565-701, Korea.
Bae
KiHwan
K
Yun
Yeo-Pyo
YP
Hong
Jin-Tae
JT
Kwon
Han-Na
HN
Oh
Ki-Wan
KW
D000098:Acetophenones / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D000284:Administration, Oral; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D003213:Conditioning, Psychological / Q000187:drug effects*; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009020:Morphine / Q000008:administration & dosage / Q000037:antagonists & inhibitors*; D009043:Motor Activity / Q000187:drug effects*; D029596:Paeonia / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D011954:Receptors, Dopamine / Q000502:physiology; D013037:Spatial Behavior / Q000187:drug effects*
D000098:Acetophenones; D018492:Dopamine Antagonists; D011954:Receptors, Dopamine; C013638:paeonol; D009020:Morphine