title: A nitric oxide synthase inhibitor (L-NAME) attenuates abstinence-induced withdrawal from both cocaine and a cannabinoid agonist (WIN 55212-2) in Planaria.
abstract: We previously reported that planarians (Dugesia dorotocephala) that have been exposed to cocaine for 1 h undergo abstinence-induced withdrawal when placed into cocaine-free, but not cocaine-containing, water. We now report that planarians also display dose-related abstinence-induced withdrawal following exposure to the synthetic cannabinoid agonist WIN 55212-2, but not its inactive enantiomer (WIN 55212-3). The withdrawal from WIN 55212-2 was manifested as a significant (P < 0.05) decrease in the rate of planarian spontaneous locomotor activity over a 5-min observation period, using a recently designed metric (pLMV). We also report that withdrawal from cocaine (80 microM) or WIN 55212-2 (10 microM) was attenuated by the selective inhibitor of nitric oxide synthesis L-NAME (L-nitro-arginine methyl ester), which had no effect of its own on pLMV. These results suggest a common NO-dependent pathway of withdrawal from cocaine and WIN 55212-2 in Planaria.
authors.affiliation: Temple University School of Pharmacy, Philadelphia, PA 19140, USA. scott.rawls@temple.edu
authors.forename: Scott M
authors.initials: SM
authors.lastname: Rawls
authors.forename: Tonatiu
authors.initials: T
authors.lastname: Rodriguez
authors.forename: David A
authors.initials: DA
authors.lastname: Baron
authors.forename: Robert B
authors.initials: RB
authors.lastname: Raffa
mesh_terms: D000704:Analysis of Variance; D000779:Anesthetics, Local; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D048588:Benzoxazines; D002186:Cannabinoids / Q000819:agonists; D003042:Cocaine; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D009025:Morpholines / Q000633:toxicity*; D009043:Motor Activity / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000627:therapeutic use*; D009281:Naphthalenes / Q000633:toxicity*; D010932:Planarians / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D013997:Time Factors
chemical_list: D000779:Anesthetics, Local; D048588:Benzoxazines; D002186:Cannabinoids; D004791:Enzyme Inhibitors; D009025:Morpholines; D009281:Naphthalenes; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D003042:Cocaine; D019331:NG-Nitroarginine Methyl Ester