Blockade of striatal mu opioid receptors attenuates methamphetamine‐induced conditioned place preference

Abstract

The behavioral effects of METH are mediated by the striatum, which is involved in habit learning and reward association. The striatum can be 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 activation of the patch compartment relative to the matrix compartment. The patch compartment contains a high density of mu opioid receptors, while the matrix compartment expresses very few mu opioid receptors, and localized blockade of patch‐based mu opioid receptors prior to METH treatment attenuates enhanced activity of the patch compartment and reduces repetitive behavior. However, while numerous studies have examined patch‐enhanced activity and the contribution of patch‐associated mu opioid receptors to METH‐induced repetitive behavior, it is currently not known whether patch‐enhanced activity occurs during METH‐mediated reward, nor is it known if patch‐based mu opioid receptors contribute to METH reward. The goal of this study was to determine if blockade of patch‐based mu opioid receptors alters METH‐induced conditioned place preference (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 mu‐specific antagonist CTAP (0.8 mg/ml) or vehicle prior to conditioning with METH (2 mg/kg) or saline. Animals were tested for preference 24h after the last day of conditioning, sacrificed and the brains processed for immunohistochemistry. Blockade of patch‐based mu 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 mu opioid receptors contribute to this phenomenon.Support or Funding InformationDA025303 (KAH)