Choice impulsivity after repeated social stress is associated with increased perineuronal nets in the medial prefrontal cortex

Abstract

Repeated stress can predispose to substance abuse. However, behavioral and neurobiological adaptations that link stress to substance abuse remain unclear. This study investigates whether Intermittent Social Defeat (ISD), a stress protocol that promotes drug-seeking behavior, alters intertemporal decision-making and cortical inhibitory function in the medial prefrontal cortex (mPFC). Male Long Evans rats were trained in a delay discounting task (DDT) where rats make a choice between a fast (1s) small reward (1 sugar pellet) and a large (3 sugar pellets) reward that comes with a time delay (10 or 20s). A decreased preference for delayed rewards was used as an index of choice impulsivity. Rats were exposed to ISD and tested in DDT 24 hours after each stress episode, and one-and two-weeks after the last stress episode. Immunohistochemistry was performed in rats brains to evaluate perineuronal nets (PNNs) and parvalbumin GABA interneurons (PV) labeling as markers of inhibitory function in the mPFC. In the DDT, ISD significantly decreased the preference for delayed large rewards, in the short and long term. ISD also increased the density of PNNs in the mPFC. These results suggest that increased choice impulsivity and cortical inhibition predispose animals to seek out rewards after stress.