The reward circuitry in adolescence is still under construction
Department of Psychiatry and of Neurology and Neurosurgery, McGill University, Montreal, Quebec, Canada
Douglas Mental Health University Institute, Montreal, Quebec, Canada
Reward processing differs substantially between adolescents and adults, but the cellular and molecular mechanisms mediating this difference remain largely unknown. Understanding the developmental processes that are ongoing in reward-relevant circuitries during adolescence and how these events are impacted by experience, including drugs of abuse and stressors, may shed light on this question. This talk focuses on the adolescent maturation of mesocorticolimbic dopamine neurons and on the emerging role of the Netrin-1 guidance cue system and its microRNA regulators in the gradual unfolding of dopamine connectivity during this age, including dopamine axon tagging and pathfinding. I also discuss (i) how drugs of abuse and chronic social stress in adolescence alter these developmental events, inducing susceptibility or resilience later on in life and (ii) how sex, dose, and specific age within adolescence modify these effects.
Interestingly, the Netrin-1 system continues to be expressed in the adult brain and is also involved in the plasticity of the adult mesocorticolimbic dopamine circuitry induced by drugs of abuse or chronic stressors. However, the direction, magnitude, and enduring consequences of these adult effects are opposite from those observed in adolescence. We propose that the developmental cellular and molecular processes that are ongoing in reward-relevant circuitries in adolescence could explain the reward processing differences in adolescents versus adults and to be intimately connected with the immediate and enduring effects of experiences on reward sensitivity.