Prelimbic cortex and nucleus accumbens core resting state signaling dynamics as a biomarker for cocaine seeking behaviors

Abstract

Substance use disorders (SUDs) are characterized by maladaptive signaling in the prefrontal cortex and associated regions, however precisely how these drug-induced abnormalities may be linked to drug seeking/taking behaviors is not well understood. Here, in vivo local field potential (LFP) electrophysiology was used in rats to examine the relationship between overall spontaneous (resting state) activity within the prelimbic cortex (PrL) and nucleus accumbens (NAc) core, and their functional connectivity, to cocaine taking and seeking behaviors. Adult, male Sprague-Dawley rats were trained to self-administer either intravenous cocaine (0.33 mg/inf) or water reinforcement during 6-hour daily sessions over 2 weeks; extinction sessions were completed immediately after self-administration training and following 30 days experimenter-imposed abstinence. Rest LFP recordings were completed during 3 recording periods (15 min each in a chamber different from the self-administration context) conducted (1) prior to self-administration training (rest LFP 1) (2) immediately after 2 weeks of self-administration training (rest LFP 2) and (3) following 1 month abstinence (rest LFP 3). Our findings show that resting state LFP power in the PrL recorded prior to training (Rest LFP 1) was positively correlated with total cocaine intake and escalation of cocaine seeking at the beta frequency range. Immediately after self-administration training (Rest LFP 2) power in the NAc core at gamma frequency was negatively correlated with incubation of cocaine craving. For rats trained to self-administer water, no significant correlations were observed. Together, these findings show that resting state LFP at specific timepoints in the addiction cycle can serve as unique predictors (biomarkers) of cocaine use disorders.