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

Life Sci. 2019 Jan 15;217:25-33. doi: 10.1016/j.lfs.2018.11.058. Epub 2018 Nov 28.


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 (Aβ), tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β) levels in brain cortex; and the hippocampus regions were examined by immunohistochemical methods.

Key findings: In the OKA group, caspase-3, phosphorylated tau (ser396), Aβ, IL-1β 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.

Keywords: Alzheimer's disease; Cannabinoid type 2 receptor; JWH-133; Okadaic acid.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Cannabinoids / therapeutic use*
  • Male
  • Memory Disorders / chemically induced
  • Memory Disorders / drug therapy*
  • Memory Disorders / metabolism
  • Memory Disorders / pathology
  • Neuroprotective Agents / therapeutic use*
  • Okadaic Acid
  • Rats, Sprague-Dawley
  • Receptor, Cannabinoid, CB2 / agonists*
  • Receptor, Cannabinoid, CB2 / metabolism
  • Spatial Memory / drug effects*
  • tau Proteins / metabolism


  • Cannabinoids
  • Neuroprotective Agents
  • Receptor, Cannabinoid, CB2
  • tau Proteins
  • Okadaic Acid
  • 1,1-dimethylbutyl-1-deoxy-Delta(9)-THC