Exercise as a Neurobiological Intervention: Utilizing NAc Circuitry to Combat Addiction

Preclinical evidence demonstrates that various forms of exercise can attenuate conditioned place preference (CPP) and self-administration of psychostimulants and opioids. However, the underlying neurobiological mechanisms behind how exercise attenuates drug CPP and self-administration remains unclear. Of particular interest is the role of dopamine receptor-expressing medium spiny neurons (MSNs) in the nucleus accumbens (NAc), as their activity becomes dysregulated after chronic substance use. Functional differences in D1R and D2R MSNs has been observed alongside neurobiological adaptations related to exercise and drug-seeking behaviors. Here, we review mainly preclinical evidence for exercise attenuating psychostimulant and opioid CPP and self-administration along with observed neurobiological adaptations in NAc circuitry. Additionally, we propose utilizing miniscopes to further parse the role of D1R and D2R MSNs during exercise and drug self-administration in vivo.