Nicotine prevents striatal dopamine loss produced by 6-hydroxydopamine lesion in the substantia nigra.
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-microg 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 microg 6-OHDA produced an almost complete depletion of dopamine in the SN, 6 microg decreased dopamine levels by 50%. Subcutaneous nicotine (1 mg/kg) administered 4 h before and 20, 44 and 68 h after 6 microg 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-microg 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.
Costa
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División Neuroquímica, Instituto de Investigaciones Biológicas Clemente Estable, Avda. Italia 3318, 11 600, Montevideo, Uruguay.
Abin-Carriquiry
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JA
Dajas
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D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D002714:Chlorisondamine / Q000008:administration & dosage; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004195:Disease Models, Animal; D004298:Dopamine / Q000172:deficiency / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D007279:Injections, Subcutaneous; D008297:Male; D018696:Neuroprotective Agents / Q000008:administration & dosage; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D018733:Nicotinic Antagonists / Q000008:administration & dosage; D016627:Oxidopamine; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013378:Substantia Nigra / Q000187:drug effects* / Q000378:metabolism
D018696:Neuroprotective Agents; D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D015102:3,4-Dihydroxyphenylacetic Acid; D009538:Nicotine; D016627:Oxidopamine; D002714:Chlorisondamine; D004298:Dopamine