Abstract
The concepts of allostatic load, a pathologic response of allostasis, which is an adaptive process that restores homeostasis after acute stress, and overload, a dramatic increase in the allostatic load that predisposes to disease, have been extensively described in the literature. Herein we present data to support the hypothesis that some allostatic states (chronic regulatory system digressions away from its regular functioning level) may represent adaptive, rather than pathologic, mechanisms to deal with chronic anxiety and stress. In a rat model, we demonstrate that chronic stress induces adaptive changes in the lymbic-hypothalamic-pituitary-adrenal axis, and in lactate and glutamate/glutamine metabolism. Compared to rats with passive defensive response to stress, rats with active (offensive) responses had lower anxiety and plasma glucocorticoid levels, and increased lactate and decreased glutamate in the amygdala. These data suggest that allostatic states may represent adaptive endogenous autonomic nervous system strategies to calm the animal and restore homeostasis following chronic fear and stress. Funding: This study was supported by the Russian Science Foundation (grant #17-15013418), and institutional funds from the State University of New York (SUNY) Upstate Medical University. This is a TransCampus project. This work was implemented using the equipment of the Center for Genetic Resources of Laboratory Animals at ICG SB RAS, supported by the Ministry of Education and Science of Russia (Unique identifier of the project RFMEFI62117X0015). Declaration of Interest: All authors declare that there are no financial interests and no conflicts of interest. Ethical Approval: The study protocol was approved by the Committee for Bioethics and Humane Treatment of Laboratory Animals at South Ural State University, Russia.
Highlights
Many physiologic and behavioral consequences of homeostatic adaptations during chronic stress, and differences between homeostatic and allostatic regulation— as regards the limbic hypothalamic pituitary adrenal (LHPA) axis—remain undefined
There was a significant influence of behavioral phenotype in response to predator scent stress (PSS) on a relative number of branch entries [F(2,25) = 10.84, p < 0.001], exploring [F(2,25) = 14.3, p < 0.001], and time [F(2,25) = 21.04, p < 0.0001] in open arms (OA)
PSS led to increased OA entries, OA exploring, and OA times in the active offensive response (AOR) rats vs. the passive defensive response (PDR) rats or unstressed controls
Summary
Many physiologic and behavioral consequences of homeostatic adaptations during chronic stress, and differences between homeostatic and allostatic regulation— as regards the limbic hypothalamic pituitary adrenal (LHPA) axis—remain undefined. Advancing knowledge in these areas has the potential to significantly increase our understanding and treatment of stress and stress-related disorders, such as post-traumatic stress disorder (PTSD). Biological changes that occur during the adaption and exhaustion stages are referred to as allostasis and allostatic overload; they include activation of the LHPA axis and its downstream effector pathways, and changes in immune responses, cardiovascular and energy metabolism, and hypothalamus-mediated behavior (Korte et al, 2005). An allostatic state is defined by chronic deviation of regulatory systems away from their normal state of operation, to establish a new set point (Koob and Le Moal, 2001)
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