Examination of prelimbic cortex and nucleus accumbens core signaling dynamics as a biomarker for cocaine use disorder in a preclinical model

Abstract

The prelimbic cortex (PrL) and nucleus accumbens (NAc) core, brain regions implicated in higher order processes such as decision making and behavioral flexibility, undergo neuroadaptations following prolonged abstinence from cocaine. Critically, impairments in these processes are also observed in individuals living with substance use disorders (SUDs) and is thought to be linked with these neuroadaptations. Furthermore, there is evidence that using noninvasive brain stimulation (NIBS) techniques may be a promising treatment for SUDs. However, it is not quite clear how these abstinence-related disruptions in PrL and NAc core signaling are related to drug seeking and taking behaviors. Recent work in the Carelli lab has shown that using transcranial alternating current stimulation (tACS, a form of NIBS) was effective in reversing cocaine-induced deficits in PrL-NAc core circuit signaling and restoring impaired behavioral flexibility. The following document consists of three specific aims that used electrophysiological recording methods to investigate signaling dynamics in the PrL and NAc core following prolonged abstinence from cocaine, their relationships to drug seeking and taking behavior, and the effectiveness of tACS to restore cocaine-induced deficits in signaling and behavior.Doctor of Philosoph