Indiana University-Purdue University Indianapolis (IUPUI) / Thermoregulation system in mammal keeps their body temperature in a vital and yet narrow range of temperature by adjusting two main activities, heat generation, and heat loss. Also, these activities get triggered by other causes such as exercise or certain drugs. As a result, thermoregulation system will respond and try to bring back the body temperature to the normal range. Although these responses are very well experimentally explored, they often can be unpredictable and clinically deadly. Therefore, this thesis aims to analytically characterize the neural circuitry components of the system that control the heat generation and heat loss. This modeling approach can help us to analyze the relationship between different components of the thermoregulation system without directly measuring them and explain its complex responses in mathematical form. The first chapter of the thesis is dedicated to introducing a mathematical modeling approach of the circuitry components of the thermoregulation system in response to Methamphetamine which was first published in [1]. Later, in other chapters, we will expand this mathematical framework to study the other components of this system under different conditions such as different circadian phases, various pharmacological interventions, and exercise. This thesis is composed by materials from the following papers. ‎CHAPTER 1 uses the main idea, model, and figures from References [1]. Meanwhile, ‎CHAPTER 2 is based on [2] coauthored with me and is reformatted according to Purdue University Thesis guidelines. Also, ‎CHAPTER 3 interpolates materials from reference [3] coauthored and is reformatted to comply with Purdue University Thesis guidelines. ‎CHAPTER 4 is inserted from the reference [4] and is reformatted according to Purdue University Thesis guidelines. Finally, ‎CHAPTER 5 is based on Reference [5] and is reformatted according to Purdue University Thesis guidelines. Some materials from each of these references have been used in the introduction Chapter.