PROJECT SUMMARY
Research has shown a high prevalence of trauma-related disorders and substance use disorder (SUD) co-
occurrence. However, the mechanisms by which a traumatic event increases the vulnerability to SUD
development and relapse are unknown. It is known that the prelimbic cortex (PL) and nucleus accumbens (NAc)
core play critical roles in trauma-related disorders and SUD, but the neurophysiological changes caused in these
structures by trauma and cocaine exposure are not fully understood. This proposal aims to dissect the
mechanism by which a traumatic experience and cocaine exposure alter PL and NAc core communication in
ways that may increase vulnerability to cocaine use disorder development. The hypothesis is that a traumatic
event and cocaine exposure will cause neurophysiological changes in PL-NAc core synapses, resulting in
increased drug-seeking behavior. To test the hypothesis, we will assess the effects of fear conditioning (FC) as
a traumatic event, and cocaine exposure on cocaine-seeking behavior in male and female rats. Also, we will
analyze the synaptic changes of the PL-projecting neurons to the NAc core, using whole cell patch-clamp
electrophysiological recordings with optogenetic manipulation (Aim 1), as well as the influence of PL inactivation
on cocaine seeking (Aim 2) from cocaine-exposed rats with or without FC. Preliminary behavioral data show that
FC prior to cocaine exposure increases cue-primed reinstatement and cocaine-primed reinstatement in male
rats, providing a suitable behavioral paradigm for investigating the neurophysiological changes that occur in this
comorbidity. The findings of the proposed study will provide insight into how PL modulates the NAc core neurons
in the presence of a traumatic experience and drug exposure, to influence drug-seeking behavior.
