Blockade of patch-based μ opioid receptors in the striatum attenuates methamphetamine-induced conditioned place preference and reduces activation of the patch compartment

Abstract

The behavioral effects of methamphetamine (METH) are mediated by the striatum, which is divided into the patch compartment, which mediates limbic and reward functions, and the matrix compartment, which mediates sensorimotor tasks. METH treatment results in repetitive behavior that is related to enhanced relative activation of the patch versus the matrix compartment. The patch, but not the matrix compartment contains a high density of µ opioid receptors, and localized blockade of patch-based µ opioid receptors attenuates METH-induced patch-enhanced activity and repetitive behaviors. Numerous studies have examined patch-enhanced activity and the contribution of patch-associated µ opioid receptors to METH-induced repetitive behavior, but it is not known whether patch-enhanced activity occurs during METH-mediated reward, nor is it known if patch-based µ opioid receptors contribute to METH reward. The goals of this study were to determine if blockade of patch-based µ opioid receptors alters METH-induced conditioned place preference (CPP), as well activation of the patch and matrix compartments following METH-mediated CPP. A biased conditioning paradigm was used to assess CPP, and conditioning occurred over an 8-day period. Animals were bilaterally infused in the striatum with the µ-specific antagonist CTAP or vehicle prior to conditioning. Animals were tested for preference 24h after the last day of conditioning, sacrificed and the brains processed for immunohistochemistry. Blockade of patch-based µ opioid receptors reduced METH-induced CPP, and reduced patch-enhanced c-Fos expression in the striatum following METH-mediated CPP. These data indicate that patch-enhanced activity is associated with METH-mediated reward and patch-based µ opioid receptors contribute to this phenomenon.