Neural mechanisms underlying the development of substance use disorder and relapse vulnerability
When and Where
Speakers
Description
Substance use disorder (SUD) devastates lives and places a significant burden on the healthcare system. Despite its prevalence, effective treatment options remain limited, and the chronically relapsing nature of SUD makes long-term abstinence exceptionally difficult to achieve. This talk will present a series of preclinical studies aimed at deepening our understanding of neural mechanisms that drive the development and maintenance of SUD. First, I will describe a neural substrate within the nucleus accumbens – a crucial hub of the brain’s reward circuit – that enables drugs of abuse to hijack neural function and disrupt naturalistic goal-directed behavior. I will then outline molecular adaptations that support long-lasting relapse vulnerability in a mouse model of opioid use disorder, with a focus on an epigenetic mechanism in the ventral hippocampus – an important interface between memory and motivation. These studies integrate in vivo two-photon calcium imaging, intravenous drug self-administration, RNA sequencing, bioinformatic analyses, and CRISPR-mediated gene regulation, forming a comprehensive pipeline that has enbled us to generate new insights into how drugs of abuse access and disrupt brain circuits and behaviour. Further, our findings offer novel avenues for developing much-needed therapeutic interventions to combat SUD.