Comparison of the effects of nicotine and epibatidine on the striatal extracellular dopamine.
We compared the effects of nicotine and epibatidine on striatal extracellular dopamine and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA), by microdialysis in freely moving rats. Nicotine (0.5 mg/kg) elevated dopamine in the caudate-putamen and somewhat more in the nucleus accumbens. Epibatidine at 0.3 microg/kg reduced, and at 0.6 and 1.0 microg/kg increased, dopamine in the caudate-putamen; 2.0 and 3.0 microg/kg had no effect. Accumbal dopamine epibatidine elevated only at 3.0 microg/kg. Thus, in contrast to nicotine, epibatidine increased dopamine output in the caudate-putamen at smaller doses than in the accumbens. Both epibatidine and nicotine enhanced accumbal dopamine metabolism clearly more than that in the caudate-putamen. Also epibatidine was found to elevate 5-hydroxyindoleacetic acid (5-HIAA) in the nucleus accumbens at smaller doses than in the caudate-putamen. Similarly to what has been reported concerning nicotine, the dose-response curve of epibatidine to increase the dopamine output in the caudate-putamen was bell-shaped and clearly differed from that in the accumbens. These findings indicate that the nicotinic mechanisms controlling dopamine release and metabolism in the nigrostriatal and mesolimbic dopaminergic pathways differ fundamentally.
Janhunen
Sanna
S
Faculty of Pharmacy, Division of Pharmacology and Toxicology, University of Helsinki, P.O. Box 56, Viikinkaari 5, Helsinki FIN-00014, Finland.
Ahtee
Liisa
L
D015102:3,4-Dihydroxyphenylacetic Acid / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002421:Caudate Nucleus / Q000187:drug effects / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D005110:Extracellular Space / Q000187:drug effects / Q000378:metabolism*; D006719:Homovanillic Acid / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D011699:Putamen / Q000187:drug effects / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D019086:Bridged Bicyclo Compounds, Heterocyclic; D018722:Nicotinic Agonists; D011725:Pyridines; D015102:3,4-Dihydroxyphenylacetic Acid; D006897:Hydroxyindoleacetic Acid; D009538:Nicotine; C082748:epibatidine; D004298:Dopamine; D006719:Homovanillic Acid