Dissertation
ENDOCANNABINOID FUNCTION IN THE LATERAL HABENULA OF THE RAT: IMPLICATIONS FOR STRESS COPING, RESILIENCE, AND MONOAMINERGIC NEUROTRANSMISSION
Doctor of Philosophy (PhD), Washington State University
01/2017
Handle:
https://hdl.handle.net/2376/118010
Abstract
Research on the etiology of major depressive disorder (MDD) is driven by the growing societal influence of the disease as well as the need for more effective treatments. Stress plays an important role in the onset and severity of MDD, and this finding has led to a search for interventions to promote resiliency to stress. One brain region associated with stress resiliency is the lateral habenula (LHb). The LHb has recently received considerable attention because its dysfunction has been associated with MDD in humans and MDD-like phenotypes in animals. The endocannabinoid (eCB) system, which inhibits neurotransmitter release, has also been implicated in MDD and in resiliency to stress in both humans and animals. The present sets of studies were conducted to evaluate the role of the LHb eCB system in rodent models of acute and chronic stress using both behavioral measures as well as biochemical and electrophysiological assays to establish putative mechanisms within the LHb and in downstream nuclei which contribute to stress-induced behavioral changes. Results indicate that blockade of the LHb eCB system under conditions of acute stress increases active coping behavior, possibly via disinhibition of dopaminergic cell firing. Furthermore, chronic stress exposure changes both habenular eCB content and cannabinoid 1 receptor (CB1R) function in both male and female subjects. Changes in eCB content were associated with stress-related changes in physiology, and manipulation of the LHb CB1R prior to a chronic social stressor resulted in differential recruitment of coping behaviors. Together these findings highlight the critical role the LHb eCB system plays in the behavioral responses to acute and chronic stress, reinforcing the recent focus on this brain region and signaling system for developing treatments for stress-induced psychiatric disorders.
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Details
- Title
- ENDOCANNABINOID FUNCTION IN THE LATERAL HABENULA OF THE RAT: IMPLICATIONS FOR STRESS COPING, RESILIENCE, AND MONOAMINERGIC NEUROTRANSMISSION
- Creators
- Anthony Leigh Berger
- Contributors
- Rebecca M Craft (Advisor)Ryan J McLaughlin (Advisor)Michael M Morgan (Committee Member)
- Awarding Institution
- Washington State University
- Academic Unit
- Department of Psychology
- Theses and Dissertations
- Doctor of Philosophy (PhD), Washington State University
- Number of pages
- 164
- Identifiers
- 99900581628201842
- Language
- English
- Resource Type
- Dissertation