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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test

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Autor(es):
Sartim, Ariandra G. [1] ; Sales, Amanda J. [2] ; Guimaraes, Francisco S. [2, 3] ; Joca, Samia R. L. [3, 1, 4, 5]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Chem & Phys, Ribeirao Preto, SP - Brazil
[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pharmacol, Ribeirao Preto, SP - Brazil
[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Ribeirao Preto, SP - Brazil
[4] Aarhus Univ, Translat Neuropsychiat Unit, Aarhus - Denmark
[5] INCT, Natl Inst Sci & Translat Med, Ribeirao Preto - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF PSYCHOPHARMACOLOGY; v. 32, n. 8, p. 922-931, AUG 2018.
Citações Web of Science: 3
Resumo

Background: Cannabidiol is a non-psychotomimetic compound with antidepressant-like effects. However, the mechanisms and brain regions involved in cannabidiol effects are not yet completely understood. Brain-derived neurotrophic factor/tropomyosin-receptor kinase B/mammalian target of rapamycin (BDNF-TrkB-mTOR) signaling, especially in limbic structures, seems to play a central role in mediating the effects of antidepressant drugs. Aim: Since it is not yet known if BDNF-TrkB-mTOR signaling in the hippocampus is critical to the antidepressant-like effects of cannabidiol, we investigated the effects produced by cannabidiol (10/30/60 nmol/0.2 mu L) micro-injection into the hippocampus of mice submitted to the forced swim test and to the open field test. Methods: Independent groups received intra-hippocampal injections of rapamycin (mTOR inhibitor, 0.2 nmol/0.2 mu L) or K252 (Trk antagonist, 0.01 nmol/0.2 mu L), before the systemic (10 mg/kg) or hippocampal (10 nmol/0.2 mu L) injection of cannabidiol, and were submitted to the same tests. BDNF levels were analyzed in the hippocampus of animals treated with cannabidiol (10 mg/kg). Results: Systemic cannabidiol administration induced antidepressant-like effects and increased BDNF levels in the dorsal hippocampus. Rapamycin, but not K252a, injection into the dorsal hippocampus prevented the antidepressant-like effect induced by systemic cannabidiol treatment (10 mg/kg). Differently, hippocampal administration of cannabidiol (10 nmol/0.2 mu L) reduced immobility time, an effect that was blocked by both rapamycin and K252a local microinjection. Conclusion: Altogether, our data suggest that the hippocampal BDNF-TrkB-mTOR pathway is vital for cannabidiol-induced antidepressant-like effect when the drug is locally administered. However, other brain regions may also be involved in cannabidiol-induced antidepressant effect upon systemic administration. (AU)

Processo FAPESP: 15/01955-0 - Efeito do tratamento com inibidores de DNMTs e com antidepressivos sobre a metilação do DNA em genes candidatos envolvidos com a neurobiologia da depressão
Beneficiário:Amanda Juliana Sales
Linha de fomento: Bolsas no Brasil - Doutorado