Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania.
Cannabidiol (CBD), a Cannabis sativa constituent, may present a pharmacological profile similar to mood stabilizing drugs, in addition to anti-oxidative and neuroprotective properties. The present study aims to directly investigate the effects of CBD in an animal model of mania induced by D-amphetamine (D-AMPH). In the first model (reversal treatment), rats received saline or D-AMPH (2 mg/kg) once daily intraperitoneal (i.p.) for 14 days, and from the 8th to the 14th day, they were treated with saline or CBD (15, 30 or 60 mg/kg) i.p. twice a day. In the second model (prevention treatment), rats were pretreated with saline or CBD (15, 30, or 60 mg/kg) regime i.p. twice a day, and from the 8th to the 14th day, they also received saline or D-AMPH i.p. once daily. In the hippocampus CBD (15 mg/kg) reversed the d-AMPH-induced damage and increased (30 mg/kg) brain-derived neurotrophic factor (BDNF) expression. In the second experiment, CBD (30 or 60 mg/kg) prevented the D-AMPH-induced formation of carbonyl group in the prefrontal cortex. In the hippocampus and striatum the D-AMPH-induced damage was prevented by CBD (15, 30 or 60 mg/kg). At both treatments CBD did not present any effect against d-AMPH-induced hyperactivity. In conclusion, we could not observe effects on locomotion, but CBD protect against d-AMPH-induced oxidative protein damage and increased BDNF levels in the reversal model and these effects vary depending on the brain regions evaluated and doses of CBD administered.
Valvassori
Samira S
SS
Laboratório de Neurociências, Programa de Pós-Graduação em Ciências da Saúde, Unidade Acadêmica de Ciências da Saúde, Universidade do Extremo Sul Catarinense, Criciúma, SC, Brasil.
Elias
Guilherme
G
de Souza
Bruna
B
Petronilho
Fabrícia
F
Dal-Pizzol
Felipe
F
Kapczinski
Flávio
F
Trzesniak
Clarissa
C
Tumas
Vitor
V
Dursun
Serdar
S
Chagas
Marcos Hortes Nisihara
MH
Hallak
Jaime E C
JE
Zuardi
Antonio W
AW
Quevedo
João
J
Crippa
José A S
JA
D000661:Amphetamine / Q000494:pharmacology*; D000818:Animals; D018692:Antimanic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D001714:Bipolar Disorder / Q000139:chemically induced* / Q000188:drug therapy* / Q000517:prevention & control*; D019208:Brain-Derived Neurotrophic Factor / Q000096:biosynthesis; D002185:Cannabidiol / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D006948:Hyperkinesis / Q000139:chemically induced / Q000188:drug therapy; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D017397:Prefrontal Cortex / Q000187:drug effects / Q000378:metabolism; D050050:Protein Carbonylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D018692:Antimanic Agents; D019208:Brain-Derived Neurotrophic Factor; D015259:Dopamine Agents; D002185:Cannabidiol; D000661:Amphetamine