Dual effect of cAMP agonist on ameliorative function of PKA inhibitor in morphine‐dependent mice. (22nd August 2013)

• Record Type: Journal Article
• Authors: Seyedi, Seyedeh Y.; Salehi, Forouz; Payandemehr, Borna; Hossein, Sara; Hosseini‐Zare, Mahshid S.; Nassireslami, Ehsan; Yazdi, Behnoosh B.; Sharifzadeh, Mohammad
• Is Part Of: Fundamental & clinical pharmacology. Volume 28:Number 4(2014)
• Page Start: 445
• Page End: 454
• Publication Date: 2013-08-22
• Subjects: Pharmacology -- Periodicals; 615.1
• DOI: 10.1111/fcp.12045
• Languages: English
• ISSNs: 0767-3981

Abstract

<abstract abstract-type="main" id="fcp12045-abs-0001"> <title>Abstract</title> <p>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 n<sc>m</sc>/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 n<sc>m</sc>/mouse) significantly attenuated prominent behavioral signs of morphine withdrawal. Lower doses of bucladesine (50, 100 n<sc>m</sc>/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 n<sc>m</sc>/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.</p> </abstract>