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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Sartim, Ariandra G. [1] ; Sales, Amanda J. [2] ; Guimaraes, Francisco S. [2, 3] ; Joca, Samia R. L. [3, 1, 4, 5]
Total Authors: 4
[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
Total Affiliations: 5
Document type: Journal article
Source: JOURNAL OF PSYCHOPHARMACOLOGY; v. 32, n. 8, p. 922-931, AUG 2018.
Web of Science Citations: 3

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)

FAPESP's process: 15/01955-0 - Effect of inhibitors of DNMTs and antidepressants on DNA methylation in candidate genes involved in the neurobiology of depression
Grantee:Amanda Juliana Sales
Support Opportunities: Scholarships in Brazil - Doctorate