Brain Research 888 (2001) 336–342 www.elsevier.com / locate / bres Interactive report Nicotine prevents striatal dopamine loss produced by 1 6-hydroxydopamine lesion in the substantia nigra * Gustavo Costa, J.A. Abin-Carriquiry, Federico Dajas ´ ´ ´ Division Neuroquımica, Instituto de Investigaciones Biologicas Clemente Estable, Avda. Italia 3318, 11 600 Montevideo, Uruguay Accepted 23 October 2000 Abstract While the work of several groups has shown the neuroprotective effects of nicotine in vitro, evidences for the same effects in vivo are controversial, mainly regarding neuroprotection in experimental models of Parkinson’s disease. In this context, we investigated the capability of various systemic administration schedules of nicotine to prevent the loss of striatal dopamine levels produced by partial or extensive 6-hydroxydopamine (6-OHDA) lesion of rat substantia nigra (SN). Eight days after 6- and 10-mg injections of 6-OHDA in the SN there was a significant decrease of dopamine concentrations in the corpus striatum (CS) and a concomitant increase in dopamine turnover. While 10 mg 6-OHDA produced an almost complete depletion of dopamine in the SN, 6 mg decreased dopamine levels by 50%. Subcutaneous nicotine (1 mg/kg) administered 4 h before and 20, 44 and 68 h after 6 mg 6-OHDA, prevented significantly the striatal dopamine loss. Administered only 18 or 4 h before or only 20, 44 and 68 h after, nicotine failed to counteract the loss of dopamine or the increase in dopamine turnover observed in the CS. Nicotine also failed to prevent significantly the decrease of striatal dopamine levels produced by the 10-mg 6-OHDA intranigral dose. Chlorisondamine, a long-lasting nicotinic acetylcholine receptor antagonist, reverted significantly the nicotinic protective effects on dopamine concentrations. These results are showing that putative neuroprotective effects of nicotine in vivo depend on an acute intermittent administration schedule and on the extent of the brain lesion.  2001 Elsevier Science B.V. All rights reserved. Theme: Disorders of the nervous system Topic: Degenerative disease: Parkinson’s Keywords: Nicotine; Dopamine; Corpus striatum; Substantia nigra; Nicotinic acetylcholine receptor; 6-Hydroxydopamine; Chlorisondamine 1. Introduction that nicotine could have a positive effect in several neuronal processes like attention, memory processing, Although initially introduced in Europe with tobacco pain, or neuroprotection [9]. The identification of more plants for medicinal purposes, nicotine has become, than 10 genes codifying the different sub-units of the through tobacco addiction, a harmful presence in our nAChR gave a structural basis for the search of specific modern societies. The physiological effects of nicotine are subunit combinations with beneficial effects in the CNS varied, affecting the peripheral (cardiovascular, neuro- [9]. muscular) and the central nervous system (CNS) [18], and Several reports have shown that there is a negative are based on its ability to mimic the actions of acetyl- correlation between smoking and the appearance of Parkin- choline at the nicotinic acetylcholine receptors (nAChR). son’s disease. These epidemiological findings gave support The deleterious effects of tobacco use have precluded a to the hypothesis of a neuroprotective role of nicotine comprehensive study of the effects of nicotine in the CNS. [12,36] and prompted the study of the effects of nicotine In recent decades, however, several studies demonstrated stimulation in several models of neurotoxicity. At present, numerous studies have confirmed the protection conferred 1 by nicotine to neuronal cultures against toxic insults like Published on the World Wide Web on 1 December 2000. excitotoxins [1,11,22,31,35,42] or b-amyloid toxicity [29]. *Corresponding author. Tel. / fax: 1598-2-487-2603. E-mail address: fdajas@iibce.edu.uy (F. Dajas). Blockade of the neuroprotection effects by nAChR antago- 0006-8993 / 01 / $ – see front matter  2001 Elsevier Science B.V. All rights reserved. PII: S0006-8993(00)03087-0