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Updated: May 24, 2026
A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Context-dependent effects of a single administration of mirtazapine on the expression of methamphetamine-induced
Robin M Voigt1, T Celeste Napier
1Department of Pharmacology, Center for Compulsive Behavior and Addiction, Rush University Medical Center Chicago, IL, USA.
Abstract:
Re-exposure to cues repeatedly associated with methamphetamine (Meth) can trigger Meth-seeking and relapse in the abstinent abuser. Weakening the conditioned Meth-associated memory during cue re-exposure may provide a means for relapse-reduction pharmacotherapy. Accordingly, we sought to determine if the atypical antidepressant mirtazapine disrupted the persistence of Meth-induced conditioned place preference (CPP) when administered in conjunction with re-exposure to contextual conditioning cues, and if this effect was altered by Meth being present during cue re-exposure. First, we evaluated the effect of mirtazapine on the maintenance of Meth-induced CPP during re-exposure to either the saline- or Meth-paired chamber 12 days after conditioning. Meth-conditioned rats subsequently administered mirtazapine expressed CPP independent of re-exposure to the saline- or Meth-paired chamber; but the magnitude of CPP was significantly less for mirtazapine-treated rats re-exposed to the Meth-paired chamber. Next, we evaluated the effect of mirtazapine on a "reinforced re-exposure" to the Meth-paired context. Administration of mirtazapine vehicle and Meth, prior to re-exposure to the Meth-paired chamber did not disrupt the ability of rats to demonstrate CPP 15 days after conditioning; however, CPP was disrupted when rats were administered mirtazapine and Meth prior to re-exposure to the Meth-paired chamber. These results indicate that the capacity of mirtazapine to diminish Meth-induced CPP is promoted if mirtazapine treatment is coupled with Meth administration in the Meth-associated context and thus appears to be the consequence of disrupting processes necessary to reconsolidate CPP following activation of drug-associated memories.
Insights
Mirtazapine can reduce methamphetamine-associated memories and drug seeking. Combining mirtazapine with methamphetamine during re-exposure to drug cues enhances its relapse-reduction effects by disrupting memory reconsolidation.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Re-exposure to drug-associated cues triggers relapse in abstinent individuals.
- Weakening these conditioned memories during cue re-exposure may reduce relapse.
- Methamphetamine (Meth) addiction is a significant public health concern.
Purpose of the Study:
- To investigate if mirtazapine disrupts methamphetamine-induced conditioned place preference (CPP).
- To determine if Meth presence during cue re-exposure alters mirtazapine's effect.
- To explore mirtazapine's potential as a relapse-reduction pharmacotherapy.
Main Methods:
- Rats were conditioned to associate methamphetamine with specific chambers.
- Mirtazapine or vehicle was administered during re-exposure to conditioned cues.
- CPP was assessed after re-exposure, with or without concurrent methamphetamine administration.
Main Results:
- Mirtazapine reduced CPP magnitude when rats were re-exposed to the Meth-paired chamber.
- Mirtazapine disrupted CPP when administered with Meth during re-exposure to the Meth-associated context.
- Mirtazapine's efficacy was enhanced by concurrent Meth administration during re-exposure.
Conclusions:
- Mirtazapine can diminish methamphetamine-induced CPP.
- Coupling mirtazapine treatment with Meth administration in the associated context enhances its effect.
- This suggests mirtazapine disrupts reconsolidation of drug-associated memories.
