title: Mirtazapine alters cue-associated methamphetamine seeking in rats.
abstract: BACKGROUND
  Methamphetamine (METH) is a potent psychostimulant, repeated use of which can result in a substance abuse disorder. Withdrawn individuals are highly prone to relapse, which may be driven, at least in part, by a hyperresponsivity to METH-associated cues that can prompt METH-seeking. Clinically efficacious pharmacotherapies for METH abuse are critically needed. Mirtazapine (Remeron) is an atypical antidepressant that antagonizes activated norepinephrine(α)₂, histamine₁ serotonin (5-HT)₂(A/C), and 5-HT₃ receptors. This pharmacologic profile prompted our interest in its potential for preventing relapse to METH-taking. This study tested the hypothesis that mirtazapine would attenuate METH-seeking in rats trained to self-administer METH.
  
  
  METHODS
  Rats were trained to self-administer METH in a lever-pressing operant task. The effect of mirtazapine on METH-seeking was determined by evaluating lever pressing in the presence of cues previously associated with METH, but in the absence of METH reinforcement. Two paradigms were used: cue reactivity, wherein rats do not undergo extinction training, and a cue-induced reinstatement paradigm after extinction.
  
  
  RESULTS
  Mirtazapine (5.0 mg/kg) pretreatment reduced METH-seeking by ∼ 50% in the first 15 min of cue reactivity and cue-induced reinstatement testing. This mirtazapine dose did not significantly affect motor performance.
  
  
  CONCLUSIONS
  This study revealed the overlapping nature of cue reactivity and cue-induced reinstatement procedures and provided preclinical evidence that mirtazapine can attenuate METH-seeking behavior.
authors.affiliation: Department of Pharmacology, Rush University Medical Center, Chicago, Illinois 60612, USA. Steven_graves@rush.edu
authors.forename: Steven M
authors.initials: SM
authors.lastname: Graves
authors.forename: T Celeste
authors.initials: TC
authors.lastname: Napier
mesh_terms: D000818:Animals; D000929:Antidepressive Agents, Tricyclic / Q000494:pharmacology*; D003463:Cues; D004347:Drug Interactions; D058999:Drug-Seeking Behavior / Q000187:drug effects*; D005108:Extinction, Psychological; D008297:Male; D008694:Methamphetamine / Q000008:administration & dosage / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D008803:Mianserin / Q000031:analogs & derivatives* / Q000494:pharmacology; D000078785:Mirtazapine; D009043:Motor Activity / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012646:Self Administration / Q000379:methods
chemical_list: D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D008694:Methamphetamine; D000078785:Mirtazapine