Neurological effects of cannabidiol in olanzapine/high-fat diet co-treated adult male Wistar rats

ABSTARCTThe present study investigates the neuroprotective effects of Cannabidiol (CBD) in olanzapine/high-fat diet (HFD) treated adult male Wistar rats. Animals weighing 160-180 g were divided into five groups (n = 7). They include Untreated, HFD+Olan, Met + HFD+Olan, CBD (10 mg/kg)+HFD+Olan, and CBD (25 mg/kg)+HFD + Olan. Olanzapine and metformin were administered as 5 mg/kg and 20 mg/kg, respectively. Cognitive functions, brain biochemical markers, histology and immunohistochemistry were determined. 2 weeks cotreatment of olanzapine/HFD induced cognitive impairment evidenced by significant reduction in Object location memory (OLM) from 3.5 ± 0.75 to -39 ± 8.57% and Object recognition memory (ORM) indices from 21.47 ± 12.68 to -30.30 ± 4.29%, increased serum amyloid beta 1-42 and GFAP hypothalamic and prefrontal cortex expressions. CBD comparable to metformin ameliorated the induced cognitive impairment. CBD possesses remarkable cognitive preserving activity which is associated with decreased lipid peroxidation and down regulation of GFAP/ACHE pathway.