title: Prostaglandin E2 attenuates SR141716A-precipitated withdrawal in tetrahydrocannabinol-dependent mice.
abstract: The present study aimed to clarify the role of the arachidonic acid cascade in mediating the expression of withdrawal signs in cannabinoid-dependent mice. Mice were injected with Delta(8)-tetrahydrocannabinol (THC) at 20 mg/kg (i.p.) every 12 h, 11 times. When SR141716A, a specific cannabinoid CB1 receptor antagonist, at 10 mg/kg (i.p.) was given 4 h after the last THC injection, withdrawal signs such as forepaw licking, facial preening, grooming, forepaw tremor, head shakes and weight loss were clearly observed. PGE(2) at 0.1, 1.0 and 3.2 microg (per animal; i.c.v.) given prior to SR141716A (10 mg/kg, i.p.) dose-dependently decreased the number of forepaw licking, facial preening, grooming and forepaw tremor episodes. Instead of SR141716A, a cyclooxygenase inhibitor diclofenac at 10 mg/kg (i.p.) also precipitated these withdrawal signs. The results suggest that the expression of THC withdrawal is due to a decrease in prostaglandin levels through inactivation of the arachidonic acid cascade in the brain.
authors.affiliation: Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka 812-8582, Japan.
authors.forename: Kusnandar
authors.initials: K
authors.lastname: Anggadiredja
authors.forename: Taku
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tanaka
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Shoyama
authors.forename: Shigenori
authors.initials: S
authors.lastname: Watanabe
authors.forename: Tsuneyuki
authors.initials: T
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D002186:Cannabinoids / Q000037:antagonists & inhibitors / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D013759:Dronabinol / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011720:Pyrazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug / Q000037:antagonists & inhibitors / Q000378:metabolism; D000077285:Rimonabant; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy / Q000378:metabolism*
chemical_list: D002186:Cannabinoids; D010880:Piperidines; D011720:Pyrazoles; D043882:Receptors, Cannabinoid; D011955:Receptors, Drug; D013759:Dronabinol; D015232:Dinoprostone; D000077285:Rimonabant