Adaptations in In Vivo Catecholamine Signaling in Models Of Stress and Addiction Public Deposited

Downloadable Content

Download PDF
Last Modified
  • March 20, 2019
Creator
  • Fox, Megan
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • Catecholamine neurotransmission plays a key role in regulating a variety of behavioral and physiological processes, and its dysregulation is implicated in both neurodegenerative and neuropsychiatric disorders. Understanding how catecholamine signaling is regulated in vivo may provide insight into its role in disease states ranging from anxiety and drug addiction to Parkinson’s disease. This work combines rapid, selective, and spatially resolved voltammetric measurements with pharmacology and behavior. We used this approach in divergent animal models to investigate the dynamics of in vivo norepinephrine and dopamine signaling. Our initial investigations focused on norepinephrine release in the ventral bed nucleus of the stria terminalis (vBNST), where we found differential regulation in models of anxiety and depression. When animals were challenged with social-isolation stress and drug-dependence, adaptations in vBNST norepinephrine regulation varied with respect to both stressor and baseline stress-reactivity. We hypothesized that certain stressors elicited catecholamine efflux, and turned to real-time measurements in awake, freely moving animals. To understand how release could produce plasticity in catecholamine regulation mechanisms after drug dependence, we focused on opiate exposure and withdrawal. We found opposing responses from dopamine and norepinephrine: whereas dopamine fluctuations in the nucleus accumbens (NAc) increased during morphine intoxication, they decreased during precipitated withdrawal. Conversely, increased norepinephrine overflow in the vBNST was found only during withdrawal, and was time locked to somatic withdrawal behaviors. While probing real-time catecholamine overflow, we also discovered hemispheric synchrony of NAc dopamine fluctuations, and revealed previously unappreciated cross-hemispheric projections in both the dopaminergic and noradrenergic systems. Our findings of opposing catecholamine responses, combined with genetic differences in response to stressors provide new insight into catecholamine regulation. Future work should continue to address how dopamine and norepinephrine signal in vivo and in real time and contribute to the development of a variety of neuropsychiatric conditions.
Date of publication
Keyword
Resource type
Rights statement
  • In Copyright
Advisor
  • Robinson, Donita
  • Brustad, Eric
  • Erie, Dorothy
  • Wightman, R. Mark
  • Manis, Paul B.
Degree
  • Doctor of Philosophy
Degree granting institution
  • University of North Carolina at Chapel Hill Graduate School
Graduation year
  • 2016
Language
Parents:

This work has no parents.

Items