Journal
BIOLOGICAL PSYCHIATRY
Volume 69, Issue 3, Pages 275-281Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2010.09.032
Keywords
Atypical antidepressant; cue reactivity; methamphetamine; reinstatement; self-administration
Categories
Funding
- [USPHSG DA015760]
- [DA016496]
- [DA024923]
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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 Withdrawn individuals are highly prone to relapse, which may be driven, at least in part, by a hyperresponsivity to METH-associated cues that can prompt METH-seeking.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(alpha 2), histamine(1) serotonin (5-HT)(2A/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 similar to 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.
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