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                            Library & Multimedia
 Opioid-like adverse effects of tianeptine in male rats and mice
NCJ Number
              305171
Journal

*PSYCHOPHARMACOLOGY* Volume: 239 Dated: Feb 2022 Pages: 2187-2199
Author(s)
          T. R. Baird;
                        H. I. Akbarali;
                        W. L. Dewey;
                        H. Elder;
                        M. Kang;
                        S. A. Marsh;
                        M. R. Peace;
                        J. L. Poklis;
                        E. J. Santos;
                        S. S. Negus
Date Published

February 2022
Annotation
              The present study evaluated tianeptine in a rat model of abuse potential assessment and in mouse models of motor, gastrointestinal, and respiratory adverse effects.
Abstract
              Tianeptine is a mu-opioid receptor (MOR) agonist with increasing reports of abuse in human populations. Preclinical data regarding the abuse potential and other opioid-like adverse effects of tianeptine at supratherapeutic doses are sparse. Abuse potential was assessed in adult male Sprague–Dawley rats using an intracranial self-stimulation (ICSS) procedure to determine effects of acute and repeated tianeptine on responding for electrical brain stimulation. Male ICR mice were used to determine the effects of tianeptine in assays of locomotor behavior and gastrointestinal motility. Male Swiss-Webster mice were monitored for respiratory changes using whole-body plethysmography. In rats, acute tianeptine produced weak and delayed evidence for abuse-related ICSS facilitation at an intermediate dose (10 mg/kg, IP) and pronounced, naltrexone-preventable ICSS depression at a higher dose (32 mg/kg, IP). Repeated 7-day tianeptine (10 and 32 mg/kg/day, IP) produced no increase in abuse-related ICSS facilitation, only modest tolerance to ICSS depression, and no evidence of physical dependence. In mice, tianeptine produced dose-dependent, naltrexone-preventable locomotor activation. Tianeptine (100 mg/kg, SC) also significantly inhibited gastrointestinal motility and produced naloxone-reversible respiratory depression. Tianeptine presents as a MOR agonist with resistance to tolerance and dependence in our ICSS assay in rats, and it has lower abuse potential by this metric than many commonly abused opioids. Nonetheless, tianeptine produces MOR agonist-like acute adverse effects that include motor impairment, constipation, and respiratory depression. (Publisher abstract provided)
      
  
          Additional Details
Grant Number(s)
        2019-R2-CX-0046


  
  
        
  Agencies
        NIJ-Sponsored


  
  
        
  Publication Type
        Research (Applied/Empirical)


  
  
        
  Award
        The Effects of Synthetic Cathinone Chirality on Pharmacodynamics and Pharmacokinetics and Its Implications for Forensic Toxicology
    
  
  
Date Published: February 1, 2022
    
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