The Role Of The Patch Compartment Neurons In Methamphetamine-mediated Reward

Abstract

The striatum is significantly important in the formation of habitual behaviors as well as reward association. Elicited reward behavior from methamphetamine (METH) is mediated by the striatum. Two distinct striatal sub regions, the patch and matrix, have been shown by previous studies to have key relationship in the regulation of addiction behavior. The patch compartment, in contrast with the matrix, expresses a high density of mu opioid receptors and receives dense inputs from limbic regions of the brain. Patch compartment neurons contribute to habitual behaviors, and our hypothesis is that these neurons also contribute to reward. The goal of this work was to investigate the role of the patch compartment neurons in METH-induced reward behavior. The approach was designed to determine if the ablation of mu opioid receptor-containing neurons of the patch compartment would alter METH-mediated Condition Placed Preference (CPP). This was achieved by using Dermorphin-Saporin (DERM-SAP), a neurotoxin that specifically targets and eliminates mu opioid receptor-containing neurons. Male and female rats in this study were bilaterally infused in striatum either with DERM-SAP or unconjugated Saporin (SAP), which was used as a control. After eight days of recovery, subjects were placed into the CPP paradigm, receiving either a moderate dose of methamphetamine (2mg/kg) or saline. After eight days of conditioning, a preference test was conducted on each animal. It was found that METH-mediated CPP was reduced in female rats which were pretreated with DERM-SAP, while METH-mediated CPP was increased in male rats with DERM-SAP lesions. These results allow us to conclude that patch compartment neurons are necessary for METH-induced reward behaviors in females, but not males.