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Effects of cannabidiol on amphetamine-induced oxidative stress generation in an animal model of mania

2009; SAGE Publishing; Volume: 25; Issue: 2 Linguagem: Inglês

10.1177/0269881109106925

1461-7285

Samira S. Valvassori, Guilherme Alves Elias, Bruna de Souza, Fabrícia Petronilho, Felipe Dal‐Pizzol, Flávio Kapczinski, Clarissa Trzesniak, Vítor Tumas, Serdar Dursun, Marcos Hortes Nisihara Chagas, Jaime EC Hallak, Antônio Waldo Zuardi, João Quevedo, J.A.S. Crippa,

Neurotransmitter Receptor Influence on Behavior

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.