Steven M Graves1, T Celeste Napier. 1. Department of Pharmacology, Rush University Medical Center, Chicago, Illinois 60612, USA. Steven_graves@rush.edu
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 Withdrawn individuals are highly prone to relapse, which may be driven, at least in part, by a hyperresponsivity to METH-associated cues that can prompt METH-seeking.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. Copyright Â
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 Withdrawn individuals are highly prone to relapse, which may be driven, at least in part, by a hyperresponsivity to METH-associated cues that can prompt METH-seeking.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. Copyright Â
Authors: S Grant; E D London; D B Newlin; V L Villemagne; X Liu; C Contoreggi; R L Phillips; A S Kimes; A Margolin Journal: Proc Natl Acad Sci U S A Date: 1996-10-15 Impact factor: 11.205
Authors: Philippe De Deurwaerdère; Sylvia Navailles; Kelly A Berg; William P Clarke; Umberto Spampinato Journal: J Neurosci Date: 2004-03-31 Impact factor: 6.167
Authors: Deanne M Buffalari; Nana Yaa A Marfo; Tracy T Smith; Melissa E Levin; Matthew T Weaver; Edda Thiels; Alan F Sved; Eric C Donny Journal: Pharmacol Biochem Behav Date: 2014-06-24 Impact factor: 3.533