Endogenous cannabinoid, 2-arachidonoylglycerol, attenuates naloxone-precipitated withdrawal signs in morphine-dependent mice.
In the present study, we examined the effects of endogenous ligand 2-arachidonoylglycerol (2-AG) on naloxone-precipitated withdrawal in morphine-dependent mice, in comparison with that of two cannabinoid agonists, an ingredient of Cannabis sativa Delta(8)-tetrahydrocannabinol (Delta(8)-THC) and the synthetic cannabinoid CB1 receptor agonist HU-210. 2-AG at a dose of 10 microg per mouse (i.c.v.) significantly inhibited both jumping and forepaw tremor as signs of withdrawal following naloxone challenge in morphine-dependent mice. Furthermore, both Delta(8)-THC and HU-210 significantly attenuated these symptoms of withdrawal in morphine-dependent mice. Therefore, it is suggested that inactivation of the endogenous cannabinoid system is related to the induction of withdrawal syndrome in morphine-dependent mice. Moreover, hyperlocomotor activity in morphine-dependent mice was markedly increased by Delta(8)-THC 10 mg/kg, which had no effect in naive mice. This finding suggested that in morphine dependence, upregulation of cannabinoid CB1 receptors occurred. Non-psychoactive CB1 receptor agonists or accelerators of endocannabinoid synthesis may be potential as therapeutic drugs for opiate withdrawal symptoms.
Yamaguchi
T
T
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan.
Hagiwara
Y
Y
Tanaka
H
H
Sugiura
T
T
Waku
K
K
Shoyama
Y
Y
Watanabe
S
S
Yamamoto
T
T
D000818:Animals; D001095:Arachidonic Acids; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids / Q000494:pharmacology*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D013759:Dronabinol / Q000031:analogs & derivatives* / Q000494:pharmacology; D063388:Endocannabinoids; D005989:Glycerides / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D009270:Naloxone / Q000494:pharmacology*; D009292:Narcotic Antagonists / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000819:agonists / Q000378:metabolism*; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D002186:Cannabinoids; D063388:Endocannabinoids; D005989:Glycerides; D009292:Narcotic Antagonists; D018377:Neurotransmitter Agents; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D009270:Naloxone; D013759:Dronabinol; C094503:glyceryl 2-arachidonate; C062018:HU 211