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Role of Oxytocin and GABA in the Prefrontal Cortex in Mediating Anxiety Behavior

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2017, Doctor of Philosophy, Ohio State University, Psychology.
This dissertation consists of two parts both of which aim to understand the neurobiological mechanisms underlying the anxiolytic actions of oxytocin (OT), focusing specifically on its interactions with the inhibitory neurotransmitter GABA in the medial prefrontal cortex (mPFC). Anxiety disorders affect about 40 million adults and are devastating in the personal, societal, and financial costs, yet, current treatment strategies are not completely effective which is likely related to the our limited understanding of the neural underpinnings of anxiety disorders. Both OT and GABA are well-known regulators of anxiety-like behavior. Furthermore, the mPFC has been shown to play a role in the modulation of anxiety behavior and contains OT-sensitive neurons as well as many GABAergic interneurons, some of which express OT receptors (OTR). Together, it seems likely that an OT-GABA interaction in the mPFC may play an important role in regulating anxiety but this hypothesis has not been tested. In Part 1, we examine the anxiolytic effects of exogenous OT in the mPFC and its interactions with GABA. After an introduction in Chapter 1, we assess the regional and receptor specificity of OT’s anxiolytic actions within the mPFC in Chapter 2. We confirm and extend previous work by demonstrating that infusion of OT into the prelimbic (PL) region of the mPFC, but not other regions, decreased anxiety-like behavior and show that the attenuation in anxiety-like behavior following OT administration into the PL mPFC is abolished with pretreatment with a selective OTR antagonist (OTR-A). Further, although OT has been implicated in the attenuation of the HPA axis response to stress, our results show that OT acting within the mPFC does not diminish the stress-induced glucocorticoid levels. In Chapter 3, we assess OT’s mechanism of action and demonstrate that the attenuation in anxiety-like behavior following OT administration into the PL mPFC is abolished by pretreatment with a GABAA receptor antagonist. Furthermore, OT in the mPFC increased activation of GABA neurons and was associated with altered neuronal activation in the amygdala following exposure to the enxiogenic environment of the elevated plus maze. The postpartum period is a time that is often accompanied by a natural reduction in anxiety and an upregulation of the OT and GABA systems. However, anywhere from 3-43% of women experience postpartum anxiety within the first year postpartum. Both OT and GABA are known regulators of postpartum anxiety, and just as in anxiety in the non-postpartum state, the mPFC has been shown to regulate aspects of maternal care behaviors and postpartum anxiety. Thus, in Part 2 of this dissertation we examine the anxiolytic effects of endogenous OT and GABA in the PL mPFC of postpartum females. Chapter 4 provides an overview of maternal anxiety and in Chapter 5, we show that OT acting within the PL mPFC modulates anxiety-like behavior during the postpartum period. Chapter 6 expands our investigation of postpartum anxiety to GABA by showing that blockade of GABAAR in the PL mPFC prevents the normal reduction in postpartum anxiety. Further, we demonstrate that mother-pup separation, which increases anxiety, was accompanied by decreased activation of GABAergic neurons in the PL mPFC and that reduced maternal anxiety could be restored by activation of the GABAAR in the PL mPFC. Overall, the findings from this dissertation suggest that OT and GABA act within the PL mPFC to reduce anxiety-like behavior likely in an interactive manner. In doing so, this work provides new insights into the neural circuitry and the mechanisms that underlie anxiety-like behavior.
Benedetta Leuner, PhD (Advisor)
Baldwin Way, PhD (Committee Member)
Laurence Coutellier, PhD (Committee Member)
180 p.

Recommended Citations

Citations

  • Sabihi, S. (2017). Role of Oxytocin and GABA in the Prefrontal Cortex in Mediating Anxiety Behavior [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492512470344886

    APA Style (7th edition)

  • Sabihi, Sara. Role of Oxytocin and GABA in the Prefrontal Cortex in Mediating Anxiety Behavior. 2017. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1492512470344886.

    MLA Style (8th edition)

  • Sabihi, Sara. "Role of Oxytocin and GABA in the Prefrontal Cortex in Mediating Anxiety Behavior." Doctoral dissertation, Ohio State University, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=osu1492512470344886

    Chicago Manual of Style (17th edition)