Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neuronsincreased cannabinoid CB1 receptor mRNA levels in the rat striatum: Possible therapeutic implications

It has been recently suggested that the effects of cannabinoids on motor be havior might be different in rats with lesions of the basal ganglia than co ntrols. In the present study, we have examined the possible alteration in t he status of cannabinoid CB1 receptors in the basal ganglia of rats with un ilateral lesions of nigrostriatal dopaminergic neurons caused by 6-hydroxyd opamine, an animal model of Parkinson's disease. As expected, lesioned rats exhibited a marked reduction in tyrosine hydroxylase-mRNA levels, measured by in situ hybridization, in the substantia nigra of the lesioned side. Le sioned rats also exhibited the characteristic rotational behavior after a s ingle injection of apomorphine. Interestingly, we also found a significant increase in levels of CB1 receptor-mRNA transcripts in the lesioned side in both the lateral and medial caudate-putamen, which supports a critical rol e for dopamine in the control of CB1 receptor gene expression in striatal e fferent neurons. This also suggests that CB1 receptor antagonists might be useful to improve movement in Parkinson's disease.