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Updated: Jun 6, 2026
A Protocol for Measuring Cue Reactivity in a Rat Model of Cocaine Use Disorder
Published on: June 18, 2018
Mirtazapine alters cue-associated methamphetamine seeking in rats
Steven M Graves1, T Celeste Napier
1Department of Pharmacology, Rush University Medical Center, Chicago, Illinois 60612, USA. Steven_graves@rush.edu
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 Withdrawn individuals are highly prone to relapse, which may be driven, at least in part, by a hyperresponsivity to METH-associated cues that can prompt METH-seeking.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.
