Cytisine and derivatives partially prevents the striatal dopamine decrease in an experimental model of Parkinson's disease

There is a negative correlation between smoking and the appearance ofParkinson’s disease. Several experimental evidences support the pro-tective role of nicotinic acetylcholine receptors (nAchR) against avariety of insults in cells in culture and in vivo. Utilizing the intrani-gral 6-OHDA injection model of experimental parkinsonism we havedemonstrated the protective effects of intermittent, subcutaneous nico-tine administration against striatal dopamine decrease. To study the protective capacity of other nAChRs agonists on the dopaminergic ter-minals, the same experimental paradigm was applied in the case of cyti-sine and novel brominated derivatives. An intermittent administrationof 2 mg/kg of cytisine and 1 mg/kg of 5-Br-cytisine, 4 h before and 20,44 and 68 h after 6-OHDA, significantly prevented the striataldopamine decline induced by the nigral lesion. The effect was not wellcorrelated with the a4b2 or a7 ligand binding potency and with the potency and efficacy to induce dopamine release in the corpus striatum.