Abstract
Disrupted operation of the reward circuitry underlies many aspects of affective disorders.
Such disruption may manifest as aberrant behavior including risk taking, depression,
anhedonia, and addiction. Early-life adversity is a common antecedent of adolescent
and adult affective disorders involving the reward circuitry. However, whether early-life
adversity influences the maturation and operations of the reward circuitry, and the
potential underlying mechanisms, remain unclear. Here, we present novel information
using cutting-edge technologies in animal models to dissect out the mechanisms by
which early-life adversity provokes dysregulation of the complex interactions of stress
and reward circuitries. We propose that certain molecularly defined pathways within
the reward circuitry are particularly susceptible to early-life adversity. We examine
regions and pathways expressing the stress-sensitive peptide corticotropin-releasing
factor (CRF), which has been identified in critical components of the reward circuitry
and interacting stress circuits. Notably, CRF is strongly modulated by early-life
adversity in several of these brain regions. Focusing on amygdala nuclei and their
projections, we provide evidence suggesting that aberrant CRF expression and function
may underlie augmented connectivity of the nucleus accumbens with fear/anxiety regions,
disrupting the function of this critical locus of pleasure and reward.
Keywords
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Article info
Publication history
Published online: December 24, 2019
Accepted:
December 11,
2019
Received in revised form:
November 25,
2019
Received:
September 3,
2019
Identification
Copyright
© 2019 Society of Biological Psychiatry.
