The role of the prefrontal cortex in cocaine-induced noradrenaline release in the nucleus accumbens: a computational study

: Research has extensively explored the role of the dopaminergic system in the reward circuit, while the contribution of the noradrenergic system remains less understood. This study aims to fill this gap by employing computational modeling to examine how the medial prefrontal cortex (mPFC) influences cocaine-induced norepinephrine (NE) release in the nucleus accumbens shell (NAcc), with mediation by the nucleus of the tractus solitarius (NTS) and the locus coeruleus (LC). The model replicates previously reported data on NE release in the mPFC following cocaine administration. Additionally, it predicts that NE depletion in the mPFC affects NE release in the NAcc through interactions with the NTS and LC. This work proposes a system-level hypothesis, suggesting that the mPFC regulates NE release in the NAcc by modulating the LC and NTS. These findings enhance our understanding of the neurochemical response to cocaine and offer potential directions for future addiction treatments.