Journal
BRITISH JOURNAL OF PHARMACOLOGY
Volume 163, Issue 7, Pages 1495-1506Publisher
WILEY
DOI: 10.1111/j.1476-5381.2011.01278.x
Keywords
Delta(9)-THCV; cannabinoid receptors; Parkinson's disease; 6-hydroxydopamine-lesioned rats; LPS-lesioned mice; neuroprotection
Categories
Funding
- CIBERNED [CB06/05/0089]
- MICINN [SAF2006-11333, SAF2009/11847]
- CAM [S-SAL-0261/2006]
- GW Pharmaceuticals Ltd
- GW Pharmaceuticals
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BACKGROUND AND PURPOSE Previous findings have indicated that a cannabinoid, such as Delta(9)-THCV, which has antioxidant properties and the ability to activate CB2 receptors but to block CB1, might be a promising therapy for alleviating symptoms and delaying neurodegeneration in Parkinson's disease (PD). EXPERIMENTAL APPROACH The ability of Delta(9)-THCV to reduce motor inhibition and provide neuroprotection was investigated in rats lesioned with 6-hydroxydopamine and in mice lesioned with lipopolysaccharide (LPS). KEY RESULTS Acute administration of Delta(9)-THCV attenuated the motor inhibition caused by 6-hydroxydopamine, presumably through changes in glutamatergic transmission. Moreover, chronic administration of Delta(9)-THCV attenuated the loss of tyrosine hydroxylase-positive neurones caused by 6-hydroxydopamine in the substantia nigra, through an effect related to its antioxidant properties (it was reproduced by cannabidiol -enriched botanical extract). In addition, CB2 receptor-deficient mice responded to 6-hydroxydopamine in a similar manner to wild-type animals, and CB2 receptors were poorly up-regulated in the rat substantia nigra in response to 6-hydroxydopamine. By contrast, the substantia nigra of mice that had been injected with LPS exhibited a greater up-regulation of CB2 receptors. In these animals, Delta(9)-THCV also caused preservation of tyrosine hydroxylase-positive neurones. This effect probably involved CB2 receptors as it was also elicited by the selective CB2 receptor agonist, HU-308, and CB2 receptor-deficient mice were more vulnerable to LPS lesions. CONCLUSIONS AND IMPLICATIONS Given its antioxidant properties and its ability to activate CB2 but to block CB1 receptors, Delta(9)-THCV has a promising pharmacological profile for delaying disease progression in PD and also for ameliorating parkinsonian symptoms.
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