Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats

Haley A Vecchiarelli; Maria Morena; Tiffany T Y Lee; Andrei S Nastase; Robert J Aukema; Kira D Leitl; J Megan Gray; Gavin N Petrie; Kristin J Tellez-Monnery; Matthew N Hill

doi:10.1016/j.ynstr.2022.100470

Sex and stressor modality influence acute stress-induced dynamic changes in corticolimbic endocannabinoid levels in adult Sprague Dawley rats

Neurobiol Stress. 2022 Jul 30:20:100470. doi: 10.1016/j.ynstr.2022.100470. eCollection 2022 Sep.

Authors

Haley A Vecchiarelli^{1

2

3}, Maria Morena^{4

2

3}, Tiffany T Y Lee^{4

2

3

5}, Andrei S Nastase^{1

2

3}, Robert J Aukema^{1

2

3}, Kira D Leitl^{4

2

3}, J Megan Gray^{4

2

3}, Gavin N Petrie^{1

2

3}, Kristin J Tellez-Monnery^{4

2

3}, Matthew N Hill^{4

2

3}

Affiliations

¹ Neuroscience Graduate Program, University of Calgary, Calgary, AB, T2N 4N1, Canada.
² Hotchkiss Brain Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
³ Mathison Centre for Mental Health Research and Education, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
⁴ Departments of Cell Biology & Anatomy and Psychiatry, Cumming School of Medicine, University of Calgary, Calgary, AB, T2N 4N1, Canada.
⁵ Department of Psychology, University of British Columbia, Vancouver, BC, V6T 1Z4, Canada.

Abstract

Research over the past few decades has established a role for the endocannabinoid system in contributing to the neural and endocrine responses to stress exposure. The two endocannabinoid ligands, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), both play roles in regulating the stress response and both exhibit dynamic changes in response to stress exposure. Most of this previous research, however, was conducted in male rodents. Given that, especially in rodents, the stress response is influenced by sex, an understanding of how these dynamic responses of endocannabinoids in response to stress is influenced by sex could provide insight into sex differences of the acute stress response. We exposed adult, Sprague Dawley rats to different commonly utilized acute stress modalities, specifically restraint, swim and foot shock stress. Thirty minutes following stress onset, we excised the amygdala, hippocampus and medial prefrontal cortex, corticolimbic brain regions involved in the stress response, to measure endocannabinoid levels. When AEA levels were altered in response to restraint and swim stress, they were reduced, whereas exposure to foot shock stress led to an increase in the amygdala. 2-AG levels, when they were altered by stress exposure were only increased, specifically in males in the amygdala following swim stress, and in the hippocampus and medial prefrontal cortex overall following foot shock stress. This increase in 2-AG levels following stress only in males was the only sex difference found in stress-induced changes in endocannabinoid levels. There were no consistent sex differences observed. Collectively, these data contribute to our further understanding of the interactions between stress and endocannabinoid function.

Keywords: 2-AG, 2-arachidonoyl glycerol; AEA, anandamide; CB1, cannabinoid type 1 receptor; CRH, corticotropin releasing hormone; CRH-R1, CRH receptor type 1; Corticolimbic; Endocannabinoid; FAAH, fatty acid amide hydrolase; HPA, hypothalamic-pituitary-adrenal; Rats; SEM, standard error of the mean; Sex differences; Stress; Stressor modality; THC, delta-9-tetrahydrocannabinol.