In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: Implications for Parkinson's Disease
Abin-Carriquiry, J., Costa, G., Urbanavicius, J., Cassels, B., Rebolledo-Fuentes, M., Wonnacott, S. and Dajas, F., 2008. In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: Implications for Parkinson's Disease. European Journal of Pharmacology, 589 (1-3), pp. 80-84.
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Nicotinic acetylcholine receptor agonists are considered potential pharmacological agents for Parkinson's Disease treatment, due to their ability to improve experimental Parkinson symptomatology, reduce 3,4-dihydroxy-l-phenylalanine-induced dyskinesias and stop the neurodegenerative process at an experimental level. In the present work, the ability of the nicotinic agonist cytisine and two halogenated derivatives (3-bromocytisine and 5-bromocytisine) to induce striatal dopamine release was characterized in vivo by microdialysis. Cytisine, 5-bromocytisine and nicotine were much more efficacious than 3-bromocytisine in eliciting dopamine release in response to their local application through the microdialysis probe. Moreover, the agonists were intermittently administered before and after an intranigral injection of 6-hydroxydopamine (6-OHDA), and striatal dopamine tissue levels were assessed 8 days after the lesion. Both cytisine and its 5-bromo derivative (but not the 3-bromo derivative) significantly prevented the decrease of striatal dopamine tissue levels induced by 6-OHDA. These results suggest that the efficacy of nicotinic agonists to stimulate dopamine release in vivo through presynaptic nicotinic receptors could be related to their potential to induce striatal protection.
|Creators||Abin-Carriquiry, J., Costa, G., Urbanavicius, J., Cassels, B., Rebolledo-Fuentes, M., Wonnacott, S. and Dajas, F.|
|Departments||Faculty of Science > Biology & Biochemistry|
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