The Effect Of Patch Compartment Neuronal Inhibition upon C-Fos Expression In Methamphetamine Addiction

Abstract

By assessing the nature of cFos neuronal expression in stereotypic habits associated with drug use, treatment models for methamphetamine addiction can be developed to address behavioral issues. The study focuses on the function of the striatum, which is involved in processing environmental information from the cortex to signal the appropriate behavior. Specifically, the patch compartment of the striatum is heavily implicated in addictive patterns through its high levels of mu opioid receptors and possesses an imbalance in cFos neuronal expression compared to its matrix counterpart. Addictive patterns develop through stimulus-response associations to create habit formation with inflexible behaviors, which occur automatically without cognitive processing. The study predicts that selective inhibition of the patch compartment will result in diminished habit formation and stereotypic behaviors associated with methamphetamine abuse. First, the iDREADD vector was inserted through the adeno-associated virus vector into the prelimbic cortex (PLC) and tagged with mCherry to observe the reduction in patch compartment neuronal activity. Then the animals underwent self administration with methamphetamine under a continuous and variable reinforcement schedule to promote habit formation. Aversion training took place in conditioned-place preference chambers to evaluate the inflexible nature of habit formation. Lastly, the rats were sacrificed and immunohistochemistry staining was subsequently performed to analyze cFos neuronal expression. The results indicated a decreased rate of stereotypic behavior within iDREADD infused rats when exposed to noxious stimuli, illustrating the decreased rate of habit formation. Through diminished habit formation, animals can adopt more flexible behavioral patterns to diminish the addictive potential of methamphetamine administration, which can be applied to human models in future research. Future experimentation should be conducted to evaluate the efficacy of inhibiting PLC in equalizing the patch-matrix compartment imbalance.