Cannabidiol attenuated the maintenance and reinstatement of extinguished methylphenidate-induced conditioned place preference in rats

Methylphenidate (MPH) is a mild CNS stimulant that has been used in hyperactive children, and patients with neurodegenerative and major depressive disorders. Exposure to MPH-associated cues enhances craving and arousal in drug users. On the other hand, cannabidiol (CBD) has antipsychotic potential that might be useful in alleviating symptoms of drug addiction. The aim of this study was to investigate the effect of CBD administration on extinction and reinstatement of MPH-induced conditioning place preference (CPP) in rats. Male rats received MPH (1, 2.5 or 5 mg/kg, i.p) or morphine (5 or 10 mg/kg, s.c.) during the conditioning phase. Following the establishment of CPP, during extinction training, 60 min prior to every CPP session, animals were given daily ICV CBD (10 or 50 µg/5 µl), vehicle alone (DMSO) 10% or were treatment-naïve. On the reinstatement day animals after receiving the initial dose of MPH, 0.5 mg/kg, and were placed into the CPP box to evaluate the CPP scoring for 10-min. Our findings indicated that morphine (5 and 10 mg/kg; s.c.) and MPH (1 and 2.5 mg/kg; i.p.) induced a CPP. The ICV administration of both doses of CBD (10 and 50 µg/5 µl) prevented the reinstatement of MPH-induced CPP, which displayed shorter extinction latency compared to treatment-naïve or DMSO 10% groups. Therefore, CBD’s site of action is a potential target for reducing the risk of MPH relapse; however, more investigation is required.