Feindel Brain & Mind Series: Drug/Stress Effects on D2 and mGlu5 Receptors

Abstract: Dopamine D2/3 and glutamate mGluR5 receptor systems are key regulators of reward learning, stress responsivity, and neuroplasticity, and have been strongly implicated in substance use disorders (SUDs). However, it remains unclear whether receptor alterations reflect pre-existing vulnerability or consequences of substance exposure. This lecture presents longitudinal PET findings from a high-risk cohort studied at ages 18 and 25 using [¹⁸F]fallypride (D2/3) and [¹¹C]ABP688 (mGluR5), alongside clinical and substance use assessments. The work examines neurochemical changes occurring before and after the onset of SUD and other DSM-5 disorders, and how these changes relate to substance use and stress. Results show that individuals who later developed SUD had higher striatal D2/3 receptor availability at age 18, followed by marked declines by age 25, with greater decreases associated with increased alcohol use. In contrast, mGluR5 declines were observed across emerging DSM-5 disorders and were linked to drug exposure and stress, with stress effects amplified among individuals with greater increases in drug use. Together, these longitudinal findings highlight developmental changes in dopamine and glutamate systems that help explain vulnerability, neuroadaptation, and the emergence of addiction and related psychopathology.

Bio: Maja Nikolic is a PhD candidate in Neuroscience at McGill University in the laboratory of Dr. Marco Leyton. Her research investigates how temperament, early life adversity, and mesocorticolimbic circuits interact across development to increase vulnerability to substance use disorders. She studies addiction vulnerability using longitudinal PET and fMRI in a high-risk cohort, focusing on dopamine D2/3 receptors ([18F]fallypride) and glutamate mGluR5 ([11C]ABP688) markers and their relationships with substance use, stress, and emerging psychopathology. In addition, she conducts structured clinical interviews (SCID-5) to characterize psychiatric outcomes and integrates clinical and neuroimaging data to model trajectories of risk and resilience.

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Montreal Neurological Institute – Hospital, 3801 Rue University, Montréal, Canada

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