Dose- and time-dependent effects of mirtazapine on the expression of cocaine-induced behavioral sensitization in rats

Psychiatry Res. 2017 Aug:254:301-310. doi: 10.1016/j.psychres.2017.05.006. Epub 2017 May 5.

Abstract

Relapse to cocaine use is a major problem in the clinical treatment of cocaine dependence. Antidepressant medications have been studied as potential therapeutic drugs to relieve a cocaine dependence disorder. Mirtazapine is an antidepressant implicated in reducing behavioral alterations induced by drugs of abuse. We have reported elsewhere that 30mg/kg mirtazapine administered for 30 days during cocaine extinction significantly attenuated the induction and expression of cocaine-induced locomotor sensitization and decreased the duration of the cocaine-induced locomotor effect. This study focused on exploring whether different mirtazapine dosing regimens could optimize and/or improve the effect of 30mg/kg mirtazapine administered for 30 days on cocaine-induced locomotor activity during the expression phase of behavioral sensitization. Our study revealed that the daily dosing regimen with a fixed dose of mirtazapine (30mg/kg ip) over 60 days improved the decrease in cocaine-induced locomotor activity and behavioral sensitization obtained by dosing of 30mg mirtazapine for 30 days. In addition, it showed that a dosing regimen of 30mg/Kg mirtazapine for 30 days managed to reduce cocaine toxicity. These results suggested that dosage of mirtazapine for 30 consecutive days may be an effective therapy.

Keywords: 5-HT receptors; Alpha receptors; Cocaine; Drug addiction; Locomotor sensitization; Mirtazapine; Pharmacotherapy.

MeSH terms

  • Animals
  • Antidepressive Agents, Tricyclic / administration & dosage*
  • Behavior, Animal / drug effects*
  • Cocaine / toxicity
  • Cocaine-Related Disorders / drug therapy*
  • Cocaine-Related Disorders / psychology
  • Dose-Response Relationship, Drug
  • Male
  • Mianserin / administration & dosage
  • Mianserin / analogs & derivatives*
  • Mirtazapine
  • Motor Activity / drug effects
  • Rats
  • Rats, Wistar
  • Time Factors

Substances

  • Antidepressive Agents, Tricyclic
  • Mianserin
  • Mirtazapine
  • Cocaine