Cannabidiol Modulates the Expression of Neurotrophin Signaling Pathway in Chronic Exposure Methamphetamine Rats During Abstinence Period

Several neuropsychiatric disorders such as addiction have indicated variations in the levels of neurotrophic factors. As an extremely addictive stimulant, Methamphetamine (METH) is associated with rising levels of abuse on a global scale. We have recently demonstrated that repeated intracerebroventricular (ICV) of cannabidiol (CBD), the most important non-psychotomimetic compound, can lead to diminished impairing memory and hippocampal damage caused by chronic exposure METH (CEM) in rats over the abstinence period. Furthermore, the results indicated a possible contribution of the neurotrophin signaling pathway (NSP) in regulating neurogenesis and survival. The next study was intended to evaluate whether these remained effects as measured in molecular pathway after abstinence period. In this regard, animals were given 2 mg/kg METH twice daily for a 10-day period. Then, we adopted real-time polymerase chain reaction (PCR) throughout the 10-day abstinence period for assessing the CBD’s effect (10 and 50 μg/5 μl) on the levels of the mRNA expression of the NSP. The findings suggested that CEM, compared with the control group in the hippocampus, downregulated mRNA expression of NSP. Moreover, a dosage of 50 μg/5μl CBD may possibly enhance the mRNA expression level of BDNF/TrkB and NGF/TrkA in the hippocampus. Besides, the expression raf-1 mRNA level could be reversed significantly by both doses of CBD. According to our results, CBD may partly bring about the neuroprotective effects by modulating the NSP. These findings set forth solid evidence demonstrating that CBD is a protection factor attributed to neuropsychiatric disorders such as METH addiction.