In vivo modulation of dopaminergic nigrostriatal pathways by cytisine derivatives: implications for Parkinson's Disease.
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.
Abin-Carriquiry
J Andrés
JA
Department of Neurochemistry, Instituto de Investigaciones Biológicas Clemente Estable, Montevideo, Uruguay. abin.ja@gmail.com <abin.ja@gmail.com>
Costa
Gustavo
G
Urbanavicius
Jessika
J
Cassels
Bruce K
BK
Rebolledo-Fuentes
Marco
M
Wonnacott
Susan
S
Dajas
Federico
F
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000978:Antiparkinson Agents / Q000494:pharmacology*; D001392:Azocines / Q000494:pharmacology; D001952:Bridged-Ring Compounds / Q000494:pharmacology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D018722:Nicotinic Agonists / Q000494:pharmacology*; D016627:Oxidopamine; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D011807:Quinolizines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects / Q000378:metabolism; D017661:Receptors, Presynaptic / Q000819:agonists / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D000978:Antiparkinson Agents; D001392:Azocines; D001952:Bridged-Ring Compounds; D004298:Dopamine; D018696:Neuroprotective Agents; D009538:Nicotine; D018722:Nicotinic Agonists; D016627:Oxidopamine; D011807:Quinolizines; D011978:Receptors, Nicotinic; D017661:Receptors, Presynaptic; C438730:3-bromocytisine; D000093843:Quinolizidine Alkaloids; C004712:cytisine