Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test
| Autor: | Francisco Silveira Guimarães, Ariandra G. Sartim, Samia R. L. Joca, Amanda J. Sales |
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| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Carbazoles Hippocampus Biology Hippocampal formation Indole Alkaloids Mice 03 medical and health sciences 0302 clinical medicine medicine Animals Cannabidiol Receptor trkB Pharmacology (medical) Swimming Sirolimus Pharmacology Brain-derived neurotrophic factor Behavior Animal Depression Brain-Derived Neurotrophic Factor TOR Serine-Threonine Kinases Antidepressive Agents Psychiatry and Mental health 030104 developmental biology nervous system ESTRESSE Antidepressant Signal transduction Neuroscience Stress Psychological 030217 neurology & neurosurgery Signal Transduction medicine.drug Behavioural despair test |
| Zdroj: | Repositório Institucional da USP (Biblioteca Digital da Produção Intelectual) Universidade de São Paulo (USP) instacron:USP Sartim, A G, Sales, A J, Guimarães, F S & Joca, S R 2018, ' Hippocampal mammalian target of rapamycin is implicated in stress-coping behavior induced by cannabidiol in the forced swim test ', Journal of Psychopharmacology, vol. 32, no. 8, pp. 922-931 . https://doi.org/10.1177/0269881118784877 |
| ISSN: | 1461-7285 0269-8811 |
| Popis: | 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 µL) 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 µL) or K252 (Trk antagonist, 0.01 nmol/0.2 µL), before the systemic (10 mg/kg) or hippocampal (10 nmol/0.2µL) 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 µL) 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. |
| Databáze: | OpenAIRE |
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