Role of the endocannabinoid system in the dorsal hippocampus in the cardiovascular changes and delayed anxiety-like effect induced by acute restraint stress in rats

Author(s)

Hartmann, Alice ^{[1, 2]} ; Fassini, Aline ^[1] ; Scopinho, America ^[1] ; Correa, Fernando M. A. ^[1] ; Guimaraes, Francisco S. ^{[1, 2]} ; Lisboa, Sabrina F. ^{[1, 2, 3]} ; Resstel, Leonardo B. M. ^{[1, 2]}

Affiliation

^[1] Univ Sao Paulo FMRP USP, Med Sch Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil

^[2] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Ribeirao Preto, SP - Brazil

^[3] Univ Sao Paulo FCFRP USP, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil

• Document type: Journal article
• Source: JOURNAL OF PSYCHOPHARMACOLOGY; v. 33, n. 5, p. 606-614, MAY 2019.
• Web of Science Citations: 0

Abstract

Background: The dorsal hippocampus has a central role in modulating cardiovascular responses and behavioral adaptation to stress. The dorsal hippocampus also plays a key role in stress-associated mental disorders. The endocannabinoid system is widely expressed in the dorsal hippocampus and modulates defensive behaviors under stressful conditions. The endocannabinoid anandamide activates cannabinoid type 1 receptors and is metabolized by the fatty acid amide hydrolase enzyme. Aims: We sought to verify whether cannabinoid type 1 receptors modulate stress-induced cardiovascular changes, and if pharmacological fatty acid amide hydrolase inhibition in the dorsal hippocampus would prevent the cardiovascular responses and the delayed anxiogenic-like behavior evoked by restraint stress in rats via cannabinoid type 1 receptors. Methods: Independent groups received intra-dorsal-hippocampal injections of N-(piperidin-1yl)-5-(4-iodophenyl)-1-(2,4-dichlorophenyl)-4-methyl-hpyra zole-3-carboxamide (AM251; cannabinoid type 1 receptor antagonist/inverse agonist, 10-300 pmol) and/or cyclohexyl carbamic acid 3-carbamoyl-biphenyl-3-yl ester (URB597; fatty acid amide hydrolase inhibitor, 10 pmol) before the restraint stress session. Cardiovascular response during restraint stress or later behavioral parameters were evaluated. Results: Acute restraint stress altered the cardiovascular response, characterized by increased heart rate and mean arterial pressure, as well as decreased tail cutaneous temperature. It also induced a delayed anxiogenic-like effect, evidenced by reduced open arm exploration in the elevated plus maze 24 h after stress. AM251 exacerbated the stress-induced cardiovascular responses after injection into the dorsal hippocampus. In contrast, local injection of URB597 prevented the cardiovascular response and the delayed (24 h) behavioral consequences of restraint stress, effects attenuated by pretreatment with AM251. Conclusion: Our data corroborate previous results indicating that the hippocampal endocannabinoid system modulates the outcome of stress exposure and suggest that this could involve modulation of the cardiovascular response during stress exposure. (AU)

• FAPESP's process: 17/19731-6 - Identification of epigenetic mechanisms induced by stress which modulate endocannabinoid signaling and neuroimmunological mechanisms as new therapeutic targets to treat the posttraumatic stress disorder (PTSD)
• Grantee: Sabrina Francesca de Souza Lisboa
• Support Opportunities: Research Grants - Young Investigators Grants
• FAPESP's process: 16/14282-6 - Evaluation of the Cannabidiol effects under neuroimmunoendocrine and behavioral alterations induced by stress in mice
• Grantee: Alice Hartmann dos Santos
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/13721-8 - Study of the involvement of endocannabinoid system into the prefrontal medial córtex on food intake of rats.
• Grantee: América Scopinho Augusto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 14/24828-0 - Possible medial prefrontal cortex CB1 receptors NMDA receptors and nitric oxide interaction on the reconsolidation and extinction of contextual fear conditioning memory of rats
• Grantee: Leonardo Resstel Barbosa Moraes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 12/17626-7 - Cellular and molecular mechanisms involved in the role of atypical neurotransmitters in neuropsychiatric disorders
• Grantee: Francisco Silveira Guimaraes
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/00249-9 - Involvement of opioid neurotransmission of the medial amygadala in the mediation of autonomic and hormonal responses evoked by restraint stress in rats
• Grantee: Aline Fassini
• Support Opportunities: Scholarships in Brazil - Doctorate