The Role of 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 role in the regulation of addiction behavior. The patch compartment, in contrast with the matrix, expresses a high density of mu opioid receptors and receives inputs from limbic regions of the brain. Patch compartment neurons have been shown to contribute to habitual behaviors and it has been hypothesized that these neurons also contribute to reward, although this has yet to be demonstrated. The basis of this experiment was to investigate the role of the patch compartment neurons in METH‐induced reward behavior. This goal was attained by determining if the ablation of the mu opioid receptor‐containing neurons of the patch compartment would alter METH‐mediated condition place reference (CPP), which is an indicator of drug reward, by using Dermorphin‐Saporin (Derm‐Sap) which is a neurotoxin used to accurately target and eliminate mu opiate receptor‐containing neurons. Male and female rats in this study were bilaterally infused in striatum either with Derm‐Sap, or unconjugated Saporin, which was used as a control. After eight days of recovery, subjects were exposed to the CPP paradigm receiving either a moderate dose of METH (2 mg/kg) or saline. After eight days of conditioning, a preference test was conducted on each animal to determine the degree of preference for the drug‐paired chamber. It was found that METH‐mediated CPP was reduced in patch‐lesioned female rats, as compared to control animals, while METH‐mediated CPP was increased in male rats with Derm‐Sap lesions as compared to controls. These results allow us to conclude that patch compartment neurons are necessary for METH‐induced reward behaviors in females, but not males.Support or Funding InformationNavicent Health Foundation Research Award to AHThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.