title: Presynaptic involvement in the nicotine prevention of the dopamine loss provoked by 6-OHDA administration in the substantia nigra.
abstract: While nicotine, through stimulation of a specific sub-population of nicotinic acetylcholine receptors (nAChR) appears to protect cells in culture against a variety of insults, studies in vivo show controversial results. In a previous paper we have shown that in the 6-hydroxydopamine (6-OHDA) model of experimental parkinsonism, an intermittent administration schedule of nicotine (4 h before and 20, 44 and 68 h after 6-OHDA) was able to prevent the decrease of dopamine (DA) concentration in the corpus striatum (CS) provoked by the partial lesion of the substantia nigra (50% neuronal death after 6 micro g of 6-OHDA). To further analyze the mechanisms of nicotine effects, we performed a microdialysis study of striatal extracellular DA concentrations utilizing the nicotine administration schedule that was able to prevent DA decrease. Basal extracellular DA concentrations in the CS were maintained after 6-OHDA and were not modified by nicotine. Basal DOPAC levels were decreased after the neurotoxic administration. The response of extracellular DA to potassium chloride (KCl) challenge was significantly lower after 6-OHDA than in control animals. Nicotine significantly reversed this decrease. As previous studies have shown, the striatal DA terminals surviving the 6-OHDA toxic effect are able to keep extracellular DA concentrations close to normal, likely increasing DA synthesis. Nevertheless, the application of a releasing factor such as KCl shows the fragility of this equilibrium, exposing a decrease in the terminal number. Nicotine, through a further activation of tyrosine hydroxylase and DA synthesis or by prolonging the life of DA terminals, could reverse the effect of 6-OHDA.
authors.affiliation: Instituto de Investigaciones Biológicas Clemente Estable, Department of Neurochemistry, Avda Italia 3318, 11600 Montevideo, Uruguay.
authors.forename: J Andrés
authors.initials: JA
authors.lastname: Abin-Carriquiry
authors.forename: Ronald
authors.initials: R
authors.lastname: McGregor-Armas
authors.forename: Gustavo
authors.initials: G
authors.lastname: Costa
authors.forename: Jessika
authors.initials: J
authors.lastname: Urbanavicius
authors.forename: Federico
authors.initials: F
authors.lastname: Dajas