Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels

Author(s)

Sales, Amanda J. ^[1] ; Crestani, Carlos C. ^[2] ; Guimaraes, Francisco S. ^{[1, 3]} ; Joca, Samia R. L. ^{[3, 4, 5]}

Affiliation

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

^[2] Sao Paulo State Univ UNESP, Sch Pharmaceut Sci Araraquara, Lab Pharmacol, Araraquara, SP - Brazil

^[3] Univ Sao Paulo, Ctr Interdisciplinary Res Appl Neurosci NAPNA, Ribeirao Preto, SP - Brazil

^[4] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Phys & Chem, Ribeirao Preto, SP - Brazil

^[5] Aarhus Univ, Translat Neuropsychiat Unit, Dept Clin Med, Aarhus - Denmark

• Document type: Journal article
• Source: PROGRESS IN NEURO-PSYCHOPHARMACOLOGY & BIOLOGICAL PSYCHIATRY; v. 86, p. 255-261, AUG 30 2018.
• Web of Science Citations: 11

Abstract

Cannabidiol (CBD) is a compound of Cannabis sativa with relevant therapeutic potential in several neuropsychiatric disorders including depression. CBD treatment has shown significant antidepressant-like effects in different rodent preclinical models. However, the mechanisms involved in CBD-induced antidepressant effects are still poorly understood. Therefore, this work aimed at investigating the participation of serotonin (5 HT) and/or noradrenaline (NA) in CBD-induced antidepressant-like effects in the forced swimming test (FST) by: 1) testing if CBD co-administration with serotonergic (fluoxetine, FLX) or noradrenergic (desipramine, DES) antidepressants would have synergistic effects; and 2) investigating if 5 HT or NA depletion would impair CBD-induced behavioral effects. Results showed that CBD (10 mg/kg), FLX (10 mg/kg) and DES (5 mg/kg) induced antidepressant-like effects in mice submitted to FST. Ineffective doses of CBD (7 mg/kg), when co-administered with ineffective doses of FLX (5 mg/kg) or DES (2.5 mg/kg) resulted in significant antidepressant-like effects, thus implicating synergistic and/or additive mechanisms. Pretreatment with PCPA (an inhibitor of serotonin synthesis: 150 mg/kg, i.p., once per day for 4 days), but not DSP 4 (a noradrenergic neurotoxin: 1 mu g/mu l, i.c.v., 24 h before the test), reduced monoamine levels in the brain. However, only PCPA treatment abolished CBD-induced behavioral effects in FST, indicating the participation of serotonergic mechanisms. None of the treatments induced locomotor effects. Our results suggest that the antidepressant-like effect induced by CBD in the FST is dependent on serotonin levels in the central nervous system (CNS). (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