Unilateral 6-Hydroxydopamine Lesions of Nigrostriatal Dopaminergic Neurons Increased Cannabinoid CB1 Receptor mRNA Levels in the Rat Striatum: Possible Therapeutic Implications
It has been recently suggested that the effects of cannabinoids on motor behavior might be different in rats with lesions of the basal ganglia than controls. In the present study, we have examined the possible alteration in the status of cannabinoid CB1 receptors in the basal ganglia of rats with unilateral lesions of nigrostriatal dopaminergic neurons caused by 6-hydroxydopamine, 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. Lesioned rats also exhibited the characteristic rotational behavior after a single 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 role for dopamine in the control of CB1 receptor gene expression in striatal efferent neurons. This also suggests that CB1 receptor antagonists might be useful to improve movement in Parkinson’s disease.
KeywordsTyrosine Hydroxylase Substantia Nigra Lesion Side Receptor mRNA Level Nigrostriatal Dopaminergic Neuron
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- Anderson, A., Anderson, J.J., Chase, T.N. and Walters, J.R., 1995, The cannabinoid agonist WIN55,212-2 and CP55,940 attenuate rotational behaviour induced by a dopamine D1 but not a D2 agonist in rats with unilateral lesions of the nigrostriatal pathway, Brain Res. 691: 106.PubMedCrossRefGoogle Scholar
- García-Gil, L., Ramos, J.A., Rubino, T., Parolaro, D. and Fernández-Ruiz, J.J., 1998, Perinatal (δ9-tetrahydrocannabinol exposure did not alter dopamine transporter and tyrosine hydroxylase mRNA levels in midbrain dopaminergic neurons of adult male and female rats, Neurotoxicol. Teratol. 20: 549.PubMedCrossRefGoogle Scholar
- Romero, J., Berrendero, F., Pérez-Rosado, A., Manzanares, J., Rojo, A., Fernández-Ruiz, J.J., de Yébenes, J.G. and Ramos, J.A., 2000, Unilateral 6-hydroxydopamine lesions of nigrostriatal dopaminergic neurons increased CB1 receptor mRNA levels in the caudate-putamen, Life Sci. 66: 485.PubMedCrossRefGoogle Scholar