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

Amanda J Sales; Carlos C Crestani; Francisco S Guimarães; Sâmia R L Joca

doi:10.1016/j.pnpbp.2018.06.002

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

Amanda J Sales, Carlos C Crestani, Francisco S Guimarães, Sâmia R L Joca

Department of Clinical Medicine - Translational Neuropsychiatry Unit

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

85 Citations (Scopus)

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 μg/μl, 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).

Original language	English
Journal	Progress in Neuro-Psychopharmacology & Biological Psychiatry
Volume	86
Pages (from-to)	255-261
Number of pages	7
ISSN	0278-5846
DOIs	https://doi.org/10.1016/j.pnpbp.2018.06.002
Publication status	Published - 30 Aug 2018

Keywords

Antidepressant
Cannabidiol
Desipramine
Fluoxetine
Noradrenaline
Serotonin

Access to Document

10.1016/j.pnpbp.2018.06.002

Cite this

@article{e17282ef27744ba5812970f4a00c87ab,

title = "Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels",

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 μg/μl, 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).",

keywords = "Antidepressant, Cannabidiol, Desipramine, Fluoxetine, Noradrenaline, Serotonin",

author = "Sales, {Amanda J} and Crestani, {Carlos C} and Guimar{\~a}es, {Francisco S} and Joca, {S{\^a}mia R L}",

year = "2018",

month = aug,

day = "30",

doi = "10.1016/j.pnpbp.2018.06.002",

language = "English",

volume = "86",

pages = "255--261",

journal = "Progress in Neuro-Psychopharmacology & Biological Psychiatry",

issn = "0278-5846",

publisher = "Elsevier Inc.",

}

Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels. / Sales, Amanda J; Crestani, Carlos C; Guimarães, Francisco S et al.
In: Progress in Neuro-Psychopharmacology & Biological Psychiatry, Vol. 86, 30.08.2018, p. 255-261.

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review

TY - JOUR

T1 - Antidepressant-like effect induced by Cannabidiol is dependent on brain serotonin levels

AU - Sales, Amanda J

AU - Crestani, Carlos C

AU - Guimarães, Francisco S

AU - Joca, Sâmia R L

PY - 2018/8/30

Y1 - 2018/8/30

N2 - 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 μg/μl, 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).

AB - 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 μg/μl, 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).

KW - Antidepressant

KW - Cannabidiol

KW - Desipramine

KW - Fluoxetine

KW - Noradrenaline

KW - Serotonin

UR - http://www.scopus.com/inward/record.url?scp=85048731233&partnerID=8YFLogxK

U2 - 10.1016/j.pnpbp.2018.06.002

DO - 10.1016/j.pnpbp.2018.06.002

M3 - Journal article

C2 - 29885468

SN - 0278-5846

VL - 86

SP - 255

EP - 261

JO - Progress in Neuro-Psychopharmacology & Biological Psychiatry

JF - Progress in Neuro-Psychopharmacology & Biological Psychiatry

ER -

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

Abstract

Keywords

Access to Document

Other files and links

Fingerprint

Cite this