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

Abstract

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.

Multiple mechanisms involved in the large-spectrum therapeutic potential of cannabidiol in psychiatric disorders

“…This compound has been tested, however, in patients suffering from bipolar disorders, a subtype of mood disorder, in whom it was not effective in treating manic episodes [133]. Actually, this is in line with animal models, in which CBD failed to prevent hyperactivity in rodents [134].…”

Acute and chronic administration of cannabidiol increases mitochondrial complex and creatine kinase activity in the rat brain

“…The doses of CBD used in this study were based on previous studies. 16,17 Different animals were used for acute and chronic experiments. Overall, the sample comprised 40 animals.…”

Cannabidiol Modulates Fear Memory Formation Through Interactions with Serotonergic Transmission in the Mesolimbic System

“…While the precise neuroanatomical regions responsible for CBD's actions are not known, considerable evidence implicates the nucleus accumbens (NAc) as an important site for CBD's modulatory effects on various cognitive and behavioral phenomena (Guimarães et al, 2004;Bhattacharyya et al, 2009;Valvassori et al, 2011;Mijangos-Moreno et al, 2014;Pedrazzi et al, 2015). For example, CBD attenuates THCinduced dysregulation of the ventral striatum during verbal recall tasks (Bhattacharyya et al, 2009) and increases c-fos and adenosine levels in rodent NAc (Guimarães et al, 2004;Mijangos-Moreno et al, 2014).…”

“…For example, CBD attenuates THCinduced dysregulation of the ventral striatum during verbal recall tasks (Bhattacharyya et al, 2009) and increases c-fos and adenosine levels in rodent NAc (Guimarães et al, 2004;Mijangos-Moreno et al, 2014). In addition, CBD blocks amphetamine-induced oxidative stress in the NAc (Valvassori et al, 2011) and intra-NAc CBD attenuates amphetamineinduced deficits in prepulse inhibition (Pedrazzi et al, 2015;Renard et al, 2016b). Nevertheless, the precise functional and pharmacological mechanisms by which CBD may produce these effects in the mesolimbic system are not currently understood.…”