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Updated: May 30, 2026
A Conditioned Place Preference Protocol for Measuring Incubation of Craving in Rats
Published on: November 6, 2018
Repeated mirtazapine nullifies the maintenance of previously established methamphetamine-induced conditioned place
Robin M Voigt1, Amanda L Mickiewicz, T Celeste Napier
1Department of Pharmacology & Experimental Therapeutics, Loyola University Chicago Medical Center, Maywood, IL, United States. voigt@rush.edu
Abstract:
The atypical antidepressant mirtazapine enhances monoaminergic transmission; thus, mirtazapine therapy may counter the hypo-activation of monoamine systems associated with withdrawal from methamphetamine abuse. Human addiction therapy will likely require chronic administration that is given after brain and behavioral maladaptations are established. To emulate this scenario in rats, we ascertained if acute or repeated mirtazapine treatments could antagonize previously established consequences of repeated methamphetamine. Methamphetamine-induced conditioned place preference (CPP) was used, wherein methamphetamine (1mg/kg, i.p.) was administered in a unique environmental context once-daily for three days interposed by saline injections in an alternate context. Subsequently, mirtazapine (5mg/kg, i.p.) was administered in the home cage either as 10 once-daily injections or a single injection. The expression of CPP was determined in drug-free rats three days after the last mirtazapine injection. Expression of methamphetamine-induced CPP was inhibited by 10 home cage administrations of mirtazapine but not by a single injection of mirtazapine. These findings reveal that mirtazapine can inhibit the maintenance of methamphetamine-induced CPP and that treatment duration and/or treatment timing contributes to this effect of mirtazapine.
Insights
Mirtazapine therapy may help with methamphetamine abuse withdrawal. Repeated mirtazapine administration, but not a single dose, inhibited established methamphetamine-induced conditioned place preference in rats.
Area of Science:
- Neuroscience
- Pharmacology
- Addiction Research
Background:
- Methamphetamine abuse leads to hypo-activation of monoamine systems.
- Mirtazapine, an atypical antidepressant, enhances monoaminergic transmission.
- Chronic mirtazapine administration may counteract methamphetamine withdrawal effects.
Purpose of the Study:
- To investigate if mirtazapine can counteract established consequences of repeated methamphetamine exposure.
- To determine the efficacy of acute versus repeated mirtazapine treatment in antagonizing methamphetamine-induced behavioral changes.
Main Methods:
- Rats were administered methamphetamine to establish conditioned place preference (CPP).
- Mirtazapine was administered either as a single dose or 10 daily doses after CPP was established.
- CPP expression was assessed in drug-free rats after the treatment period.
Main Results:
- Repeated daily administration of mirtazapine (10 injections) significantly inhibited the expression of methamphetamine-induced CPP.
- A single injection of mirtazapine did not affect the established CPP.
- Treatment duration and timing are critical factors for mirtazapine's efficacy.
Conclusions:
- Mirtazapine can inhibit the maintenance of established methamphetamine-induced CPP.
- Chronic mirtazapine treatment shows potential for managing methamphetamine addiction.
- Further research is needed to optimize mirtazapine therapy for addiction treatment.
