title: Dual effect of cAMP agonist on ameliorative function of PKA inhibitor in morphine-dependent mice.
abstract: The present study shows interactive effects of bucladesine (db-cAMP) as a cyclic adenosine monophosphate (cAMP) agonist and H-89 as a protein kinase A (PKA) inhibitor on naloxone-induced withdrawal signs in morphine-dependent mice. Animals were treated subcutaneously with morphine thrice daily with doses progressively increased from 50 to 125 mg/kg. A last dose of morphine (50 mg/kg) was administered on the 4th day. Several withdrawal signs were precipitated by intraperitoneal (i.p.) administration of naloxone (5 mg/kg). Different doses of bucladesine (50, 100, 200 nm/mouse) and H-89 (0.05, 0.5, 1, 5 mg/kg) were administered (i.p.) 60 min before naloxone injection. In combination groups, bucladesine was injected 15 min before H-89 injection. Single administration of H-89 (0.5, 1, 5 mg/kg) and bucladesine (50, 100 nm/mouse) significantly attenuated prominent behavioral signs of morphine withdrawal. Lower doses of bucladesine (50, 100 nm/mouse) in combination with H-89 (0.05 mg/kg) increased the inhibitory effects of H-89 on withdrawal signs while in high dose (200 nm/mouse) decreased the ameliorative function of H-89 (0.05 mg/kg) in morphine-dependent animals. It is concluded that H-89 and bucladesine could affect morphine withdrawal syndrome via possible interaction with cyclic nucleotide messengering systems, protein kinase A signaling pathways, and modified related neurotransmitters.
authors.affiliation: Department of Pharmacology and Toxicology, Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, PO Box 14155-6451, Tehran, Iran.
authors.forename: Seyedeh Y
authors.initials: SY
authors.lastname: Seyedi
authors.forename: Forouz
authors.initials: F
authors.lastname: Salehi
authors.forename: Borna
authors.initials: B
authors.lastname: Payandemehr
authors.forename: Sara
authors.initials: S
authors.lastname: Hossein
authors.forename: Mahshid S
authors.initials: MS
authors.lastname: Hosseini-Zare
authors.forename: Ehsan
authors.initials: E
authors.lastname: Nassireslami
authors.forename: Behnoosh B
authors.initials: BB
authors.lastname: Yazdi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Sharifzadeh
mesh_terms: D000818:Animals; D003994:Bucladesine / Q000008:administration & dosage / Q000494:pharmacology*; D000242:Cyclic AMP / Q000819:agonists*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D007546:Isoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051379:Mice; D009021:Morphine Dependence / Q000503:physiopathology; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D013375:Substance Withdrawal Syndrome / Q000503:physiopathology / Q000517:prevention & control*; D013449:Sulfonamides / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D007546:Isoquinolines; D009292:Narcotic Antagonists; D013449:Sulfonamides; D009270:Naloxone; D003994:Bucladesine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide
keywords: GABA; NMDA; cAMP; cGMP; morphine dependence; protein kinase A; withdrawal syndrome