The
cannabinoid CB2 receptor has recently emerged as a potential anti-inflammatory target to break the self-sustaining cycle of
neuroinflammation and neurodegeneration that is associated with
neurodegenerative diseases. However, in order to facilitate the development of
cannabinoid drugs for
neurodegenerative disease, the changes that occur in the
endocannabinoid system in response to different neurodegenerative triggers needs to be elucidated. Therefore, the aim of this study was to investigate and compare the changes that occur in the
endocannabinoid system in neurotoxic and
inflammation-driven models of
Parkinson's disease. To do so, male Sprague Dawley rats were given unilateral, intra-striatal
injections of the dopaminergic
neurotoxin,
6-hydroxydopamine, or the bacterial inflammagen,
lipopolysaccharide (LPS). Animals underwent behavioural testing for motor dysfunction on Days 7, 14 and 28 post-surgery, and were sacrificed on Days 1, 4, 14 and 28. Changes in the
endocannabinoid system were investigated by qRT-PCR, liquid chromatography-mass spectrometry and immunohistochemistry. After injection of
6-hydroxydopamine or LPS into the rat striatum, we found that expression of the
CB2 receptor was significantly elevated in both models, and that this increase correlated significantly with an increase in microglial activation. Interestingly, the increase in
CB2 receptor expression in the
inflammation-driven model was significantly more pronounced than that in the neurotoxic model. Moreover,
endocannabinoid levels were also elevated in the LPS model but not the
6-hydroxydopamine model. Thus, this study has shown that the
endocannabinoid system is dysregulated in animal models of
Parkinson's disease, and has also revealed significant differences in the level of dysregulation between the models themselves. This study indicates that targeting the
CB2 receptor may represent a viable target for anti-inflammatory disease modification in
Parkinson's disease.