The mGluR5 Positive Allosteric Modulator CDPPB Does not Alter Extinction or Contextual Reinstatement of Methamphetamine-Seeking Behaviorin RatsJohn J. Widholm1, Justin T. Gass2, Richard M. Cleva2 and M. Foster Olive2*
- *Corresponding Author:
- M. Foster Olive, Ph.D.
Department of Psychology, Arizona State University
PO Box 871104, Tempe, AZ85287-1104, USA
Tel: (480) 727-5550
Fax: (480) 965-8544
Received October 17, 2011; Accepted December 20, 2011; Published December 24, 2011
Citation: Widholm JJ, Gass JT, Cleva RM, Olive MF (2011) The mGluR5 Positive Allosteric Modulator CDPPB Does Not Alter Extinction or Contextual Reinstatement of Methamphetamine-Seeking Behavior in Rats. J Addict Res Ther S1:004. doi:10.4172/2155-6105.S1-004
Copyright: © 2011 Widholm JJ, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
xtinction of drug-seeking behavior is a form of new and active learning. Facilitation of extinction learning is of clinical interest since cue exposure therapies for the treatment of addiction have largely been unsuccessful in preventing relapse, primarily due to the context specificity of extinction learning. Recently, several studies have shown that potentiation of glutamatergic transmission can facilitate extinction learning in rodent models of cocaine addiction. In this study we investigated the effects of the type 5 metabotropic glutamate receptor (mGluR5) positive allosteric modulator (PAM) 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl)benzamide (CDPPB) on the extinction and contextual reinstatement of methamphetamine-seeking behavior. Rats were trained and allowed to self-administer methamphetamine (0.1 mg/kg/infusion) in 2 hr daily sessions in Context A where self-administration chambers had distinct tactile, visual, auditory, and olfactory cues. Next, CDPPB (60 mg/kg) or vehicle was administered prior to subsequent extinction training sessions that were conducted in modified self-administration chambers (Context B) that were distinct from Context A. Following 16 days of extinction training in Context B, animals were placed back in Context A for assessment of contextual reinstatement of methamphetamine-seeking behavior. CDPPB failed to produce significant reductions in extinction responding or in the magnitude of contextual reinstatement of methamphetamine-seeking compared to vehicle treated controls. We postulate that numerous factors, including methamphetamine-induced changes in mGluR5 receptor expression or function, may have contributed to the observed lack of effects. Although these findings initially suggest that mGluR5 PAMs may be ineffective in facilitating extinction learning or preventing context-induced relapse in methamphetamine addiction, additional studies are warranted examining effects of other mGluR5 PAMs, particularly those with improved pharmacological properties and devoid of potential side effects at higher doses.