A Comprehensive Review of Experimental Models of Stress: Pragmatic Insight Into Psychoneuroimmunology

ABSTRACTPsychoneuroimmunology is a scientific discipline exploring the interconnectedness of the nervous system, emotion state, and immune system. The current review examines the distinct mechanisms through which the mind and body interact when subjected to stress. Manifestations of psychoneuroimmunological stress encompass symptoms such as depression, aggression, fear, and social withdrawal, which can exert a profound impact on physiological well‐being. Some observations suggest that humans and nonhuman animals exhibit similar stress‐related symptoms, aiding in the identification of pharmacological pathways and potential clinical implications of therapeutic interventions. Animal stress models are predicated on varying approaches aimed at eliciting a motivational state to navigate and confront aversive circumstances. The current review describes the diverse stress induction models that have been investigated internationally, incorporating an ethological perspective that involves evaluating innate and unpunished behaviors through methodologies like the elevated plus maze, elevated zero maze, light‐dark box, and open field test. Additionally, conditioned operant conflict tests, such as the Vogel conflict test, fall under the purview of learning and punishment models. This category encompasses classic conditioning models like fear conditioning, psychosocial models such as social defeat, and physical and chronic unpredictable stress paradigms. In this review, we critically evaluate existing cognitive and behavioral frameworks underpinning the development and perpetuation of stress‐related disorders, while also elucidating the impact of immune system responses on the mental and physical health of animals. The primary objective of this review is to elucidate the array of animal models employed in previous research and the testing protocols used to assess animal performance in stress induction scenarios, with the ultimate aim of reducing mortality rates among research animals.