Author: Jett Zivkovic
Zivkovic, Jett, 2024 The Thermoregulatory Response to Lithium & its Inhibition of Stress-Induced Physiological & Behavioural Changes: A Novel Mechanism of Action & Brain Pathway, Flinders University, College of Medicine and Public Health
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This thesis reveals that lithium triggers a coordinated thermoregulatory response in rodents, characterised by dose-dependent lethargy, hypothermia, and reduced locomotor activity. Lithium inhibits stress-induced brown adipose tissue thermogenesis, emotional hyperthermia, and hyperlocomotion, counteracting the physiological and behavioural responses triggered by psychological stress.
Furthermore, lithium dose-dependently inhibits cold-induced elevations in BAT sympathetic nerve activity, thermogenesis, and cardiovascular parameters, which requires the area postrema. This suggests lithium reduces sympathetic outflow from the rostral medullary region of the brain via two central pathways involving the area postrema and the hypothalamomedullary thermoregulatory network.
These findings implicate specific brain regions involved in psychological stress and stress-related psychiatric conditions, providing insights into lithium's therapeutic mechanisms and potential clinical applications.
Keywords: Lithium, mood stabiliser, bipolar disorder, mood disorders, psychiatric conditions, thermoregulation, lethargy, nausea, hypothermia, brown adipose tissue, BAT, emotional hyperthermia, locomotor activity, psychological stress, stress, sympathetic nervous system, sympathetic nerve activity, area postrema, hypothalamus, rostral medullary region, hypothalamomedullary network, therapeutic mechanisms
Subject: Medicine thesis
Thesis type: Doctor of Philosophy
Completed: 2024
School: College of Medicine and Public Health
Supervisor: Yoichiro Otsuka