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Cellular Mechanisms of Addictive Processes

Elisabeth J. Van Bockstaele, PhD

Elisabeth J. Van Bockstaele, PhD
Principal Investigator

Michelle Page, PhD

Michelle Page, PhD
Co-Investigator

Rita Valentino, PhD

Rita Valentino, PhD
Children's Hospital of Philadelphia
(Co-Investigator)

Sue Menko

Sue Menko
Collaborator

Opioid Modulation of the Coeruleo-Cortical Pathway (NIH/NIDA)

fileSchematic diagram showing potential ways in which opiates sensitize LC neurons to CRF.
Left: LC neurons without morphine. Middle: Chronic morphine may increase second-
messenger response to CRF. Right: chronic morphine might reduce internalization of CRF receptors.

Goal: To examine cellular interactions between opioids and the stress-related peptide corticotropin releasing factor in the noradrenergic nucleus locus coeruleus.

file

The interaction between the stress axis and endogenous opioid systems has gained substantial clinical interest as it is increasingly recognized that stress predisposes to opiate abuse. For example, stress has been implicated as a risk factor in vulnerability to the initiation and maintenance of opiate abuse and is thought to play an important role in relapse in subjects with a history of abuse. However, the impact of stress-opioid interactions extends beyond vulnerability to opiate abuse.

Numerous reports indicating that stress alters individual sensitivity to opiates suggest that prior stress can influence the pharmacodynamics of opiates that are used in clinical settings. Conversely, the effects of opiates on different components of the stress axis can impact on individual responsivity to stressors and potentially predispose individuals to stress-related psychiatric disorders. Because these interactions have potentially widespread clinical consequences, it is important to identify substrates of the stress response and endogenous opioid systems that interact and the specific points at which stress circuits and endogenous opioid systems intersect.

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