Cannabinoid type 2 receptor agonist JWH-133, attenuates Okadaic acid induced spatial memory impairment and neurodegeneration in rats.

AIM: Cannabinoid system has various physiological roles such as neurogenesis, synaptic plasticity and emotional state regulation in the body. The presence of cannabinoid type 2 receptor (CB2), a member of the cannabinoid system, was detected in different regions of the brain. CB2 receptor plays a role in neuroinflammatory and neurodegenerative processes. We aimed to determine the possible effect of CB2 agonist JWH-133 in Okadaic acid (OKA)-induced neurodegeneration model mimicking Alzheimer's Disease (AD) through tau pathology. MATERIALS AND METHODS: In this study, 40 Sprague Dawley male rats were divided into 4 groups (Control, Sham, OKA, OKA + JWH-133). Bilateral intracerebroventricular (icv) injection of 200 ng OKA was performed in the OKA group. In the OKA + JWH-133 group, injection of JWH-133 (0.2 mg/kg) was performed intraperitoneally for 13 days different from the group of OKA. Morris water maze test was used to evaluate the spatial memory. Levels of caspase-3, phosphorylated tau (ser396), amyloid beta (Aß), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1ß) levels in brain cortex; and the hippocampus regions were examined by immunohistochemical methods. KEY FINDINGS: In the OKA group, caspase-3, phosphorylated tau (ser396), Aß, IL-1ß levels were higher in the cortex and hippocampus than in the other groups. The implementation of the JWH-133 reversed the increments in these parameters, and also prevented spatial memory impairment. SIGNIFICANCE: In this study, we found that the administration of the CB2 receptor agonist JWH-133 in this study reduced neurodegeneration, neuroinflammation, and spatial memory impairment in the OKA-induced Alzheimer's Disease model.