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

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

Differential behavioral effects of abstinence from cocaine self-administration in cued and uncued delay-based decision making tasks

Decision making is an important cognitive process that can become dysfunctional when exposed to drugs of abuse. Those who suffer from substance use disorders often have increased rates of impulsivity, including delay discounting, a type of impulsivity comprised of magnitude and delay. Studies show prior cocaine experience can elicit differential behavioral effects related to magnitude of reward, and in the presence of a discrete cue shifts behavior towards the optimal reward. Here, we developed and tested two tasks to determine if delay-based decision making is similarly influenced by discrete cues. In the cued task, animals with prior cocaine self-administration were faster to press for reward, while in the uncued task, this effect disappeared. However, cocaine history had no effect on free choice behavior in either task. These findings indicate the presence of a discrete cue influences latency to respond, but not free choice behavior, in a delay-based decision making task.Master of Art