Original Research ARTICLE
Context-dependent effects of a single administration of mirtazapine on the expression of methamphetamine-induced conditioned place preference
- 1 Department of Pharmacology, Center for Compulsive Behavior and Addiction, Rush University Medical Center, Chicago, IL, USA
- 2 Department of Molecular Pharmacology and Therapeutics, Loyola University Chicago Medical Center, Maywood, IL, USA
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.
Keywords: methamphetamine, psychostimulant, mirtazapine, addiction, conditioned place preference, associative learning
Citation: Voigt RM and Napier TC (2011) Context-dependent effects of a single administration of mirtazapine on the expression of methamphetamine-induced conditioned place preference. Front. Behav. Neurosci. 5:92. doi: 10.3389/fnbeh.2011.00092
Received: 15 October 2011;
Accepted: 27 December 2011;
Published online: 13 January 2012.
Edited by:Martine Ammassari-Teule, Consiglio Nazionale delle Ricerche, Italy
Reviewed by:Gregg Stanwood, Vanderbilt University, USA
Pascale Gisquet-Verrier, Le Centre National de la Recherche Scientifique, France
Simona Cabib, Università Sapienza Roma, Italy
Copyright: © 2012 Voigt and Napier. This is an open-access article distributed under the terms of the Creative Commons Attribution Non Commercial License, which permits non-commercial use, distribution, and reproduction in other forums, provided the original authors and source are credited.
*Correspondence: T. Celeste Napier, Department of Pharmacology, Rush University Medical Center, Cohn Research Building, 1735 West Harrison Street, Suite #424, Chicago, IL 60612, USA. e-mail: firstname.lastname@example.org
†Present address: Robin M. Voigt, Section of Digestive Diseases and Nutrition, Division of Gastroenterology, Department of Gastroenterology, Rush University Medical Center, Chicago, IL, USA.