Are Changes in the Wnt/β-Catenin Pathway Involved in Cocaine and Stress-Induced Long-Term Neuroadaptations?
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2017-10-03
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Elyns Group
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Descripción
Drug addiction has been defined as a chronic relapsing brain disease,
characterized by compulsive drug seeking and use, despite harmful
consequences. This phenomenon has been extensively studied and the
use of animal models has contributed to elucidate neurobiological bases
of the different stages in the addiction process. For the past years, we
have been studying the role of the Wnt (Wingless-related integration
site) pathways in cocaine-induce neuroadaptations by using the
behavioral sensitization paradigm to model addiction-like behaviors.
The Wnt pathways are critical during the development of both the
central and peripheral nervous systems. In particular, we centered our
attention on the Wnt/β-catenin or canonical pathway. This pathway
mediates the stabilization and nuclear translocation of the final effector
β-catenin, where it can promote the expression of different target
genes. Our findings reveal a specific spatiotemporal participation of the
Wnt/β-catenin pathway in cocaine-induced behavioral sensitization.
We found that while the initiation or development of sensitization
involves an inhibition in the Prefrontal Cortex’s canonical pathway,
the expression is related with activation in the Nucleus Accumbens.
Furthermore, we recently discover that stress during adolescence has
an impact on cocaine-induced effect in adulthood. Intriguingly, we also
found that the exposure to this early life stress influence the activity
of the Wnt/β-catenin pathway, proposing that this signaling pathway
could be mediating the proactive effect of stress on drug properties.
In this manuscript, we cover different mechanisms that may underlie
cocaine- and stress-induced changes in the Wnt canonical pathway. We
also revise the idea of this pathway as a common target for adolescent
stress and for the vulnerability to drug abuse later in life. We suggest
that the canonical Wnt pathway constitutes a promising target that may
open a door to new therapeutic strategies for the treatment of cocaine
addiction.
Palabras clave
Cocaine, Sensitization, Stress, Vulnerability to Addiction