Mirtazapine, a noradrenergic and specific serotonergic antidepressant, attenuates morphine dependence and withdrawal in Sprague-Dawley rats

Am J Drug Alcohol Abuse. 2008;34(5):541-52. doi: 10.1080/00952990802183921.


The effects of mirtazapine, a noradrenergic and specific serotonergic antidepressant, on morphine withdrawal and morphine conditioned place preference (CPP) were investigated in rats. Our results showed that some morphine withdrawal signs, including teeth chattering, grooming, chewing, and escape attendance, were attenuated by single pretreatments with 3, 10, or 30 mg/kg mirtazapine. Wet-dog shakes, rearing, and grooming were inhibited by daily pretreatment with 1, 3, or 10 mg/kg mirtazapine. The expression of morphine-induced CPP was significantly blocked by mirtazapine (10 or 30 mg/kg, i.p.), while chronic treatment with mirtazapine (1 or 10 mg/kg, i.p. once, daily, for six consecutive days) significantly attenuated the acquisition of morphine CPP. Our results demonstrated that mirtazapine attenuates morphine withdrawal and morphine-induced CPP in rats and suggest that mirtazapine may have therapeutic potential in the treatment of opiate dependence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / administration & dosage
  • Antidepressive Agents, Tricyclic / pharmacology*
  • Conditioning, Operant / drug effects
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Male
  • Mianserin / administration & dosage
  • Mianserin / analogs & derivatives*
  • Mianserin / pharmacology
  • Mirtazapine
  • Morphine / adverse effects
  • Morphine Dependence / drug therapy*
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology
  • Substance Withdrawal Syndrome / drug therapy*


  • Antidepressive Agents, Tricyclic
  • Serotonin Receptor Agonists
  • Mianserin
  • Morphine
  • Mirtazapine