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Investigating Changes in Monoamine Transmission Induced by Stress
- Dagher, Merel
- Advisor(s): Andrews, Anne M
Abstract
The serotonin system, among other neurotransmitter systems, plays an important role in mood and anxiety disorders. Stress, which is the biggest risk factor for the development of mood and anxiety disorders, leads to many lifelong changes that affect the overall function of monoamine transmission and behavior. My dissertation work set out to investigate (1) the effects of in utero stress exposure on neurochemistry and behavior during adulthood and whether concomitant maternal citalopram treatment rescued adverse stress effects, (2) the selectivity of optogenetically stimulating dopamine neurons and the interplay between monoamine systems, (3) SERT genotypes on freezing behaviors after ambiguous cue presentation, and (4) neuroinflammation produced by biosensors to monitor neurotransmitters in vivo. The primary investigation of my graduate work was focused on effects of in utero stress exposure and whether treatment with citalopram could mitigate the adverse effects of stress. To investigate this question, I used a mouse model in which pregnant dams underwent a chronic stress paradigm during their pregnancy. Some dams received concomitant treatment with citalopram, an SSRI. I then examined developmental neurochemistry, and adult neurochemical and behavioral changes. I found that pups from the stressed group had elevated neurochemical and amino acid tissue levels. Moreover, I found that pups born to stressed dams had increases in anxiety- and depressive- like behavior and that these effects were rescued in pups that received concomitant in utero citalopram exposure. Finally, stressed pups had increased serotonin concentrations after SERT blockade in the vHPC and after a systemic injection of a kappa opioid receptor agonist. My findings suggest beneficial outcomes when treating stress during pregnancy on overall offspring health.
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