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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF PSYCHOPHARMACOLOGY; v. 33, n. 5, p. 606-614, MAY 2019.
• Citações Web of Science: 0

Resumo

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)

• Processo FAPESP: 17/19731-6 - Identificação de mecanismos epigenéticos induzidos por estresse que modulam a sinalização endocanabinóide e a resposta neuroimunológica como novos alvos farmacológicos no tratamento do transtorno de estresse pós-traumático (PTSD)
• Beneficiário: Sabrina Francesca de Souza Lisboa
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores
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• Modalidade de apoio: Bolsas no Brasil - Doutorado
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• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
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• Modalidade de apoio: Auxílio à Pesquisa - Temático
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