Dynamic modulation of inhibition ability following repeated exposures to morphine in macaque monkey

Background: Deficits in cognitive control, particularly inhibition ability, play crucial roles in susceptibility, progress, and relapse to opioid addiction. However, it is unclear when and how such deficits develop and interact with repeated exposures to prescribed opioids. Aim: Using macaque monkey (Macaca mulatta), as an animal model with high translational merits in cognitive neuroscience, we tried to delineate alterations of inhibition ability in the course of repeated exposures to morphine. Methods: Monkeys were trained to perform stop-signal task and then we closely monitored their inhibition ability before exposure, after initial exposure, and following repeated exposures to morphine when they experienced abstinent periods. We also assessed morphine-induced conditioned place preference (CPP) in these monkeys to monitor the long-lasting effects of morphine on other behaviors. Results: Compared to the baseline level, monkeys' inhibition ability was significantly enhanced after initial exposure to morphine (early phase); however, it became significantly attenuated after repeated exposures (late phase). These alterations occurred while monkeys consistently expressed the morphine-induced CPP over the course of morphine exposure. Conclusions: Our findings indicate that repeated and scheduled exposures to morphine, which is akin to its clinical and recreational use, lead to dynamic alterations in primates' cognitive control depending on the extent of exposure. Enhancement of inhibition after limited exposure might provide opportunities to intervene and prevent the progress and culmination of opioid addiction, which is characterized by disinhibited drug-seeking and consumption.