Sex differences in the expression of MOR in areas critical for fear conditioning and extinction learning (LB557)

Abstract

The mu opioid receptor (MOR) has a significant role in fear conditioning and extinction learning. Communication between amygdala, periaqueductal gray (PAG) and medial prefrontal cortex (mPFC) regulates fear conditioning and extinction. Fear conditioned female rats during the metaestrus (M, low hormones) stage of the estrous cycle, showed impaired extinction while rats during the proestrus (P, high hormones) stage showed normal extinction learning. We aim to elucidate how opioid modulators alter MOR expression during fear conditioning and extinction in both sexes. Female rats on M or P stages and males rats underwent auditory fear conditioning and immediately received MOR agonist morphine, or antagonist naloxone or saline. The next day rats received extinction trials. Western blots were used to measure MOR expression. In the PAG, female rats showed no change with either treatment. In male rats morphine produced an increase in MOR expression while naloxone had an opposite effect. In the PFC, morphine during P decreased MOR expression while naloxone had no effect. Increased MOR expression was observed in the amygdala of male rats after either morphine or naloxone treatments, while in females an increase in MOR was only observed during P. Our data portraits sex differences in MOR expression in the fear circuitry, which might be responsible for the persistence of fear responses during low ovarian hormone stages. Grant Funding Source: Supported by Molecular and Genomics core RR003050, Behavioral Core Facilities MD007579 , HPD335698 Nova Southeastern University to Edwin Santini and Dinah Ramos‐Ortolaza