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Disposition of nicotine and cotinine in rat blood and brain tissue, and their effects on striatal concentrations of dopamine and serotonin
Author(s) -
Chang Y. L.,
Tsai P. L.,
Hung L. C.,
Chou Y. C.,
Tien J. H.,
Tsai T. H.
Publication year - 2005
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/j.clpt.2004.12.148
Subject(s) - cotinine , serotonin , nicotine , disposition , dopamine , pharmacology , medicine , endocrinology , anesthesia , psychology , receptor , social psychology
Background Concentrations of nicotine and cotinine following peripheral administration of nicotine to rats were determined to assess nicotine disposition in both brain and blood. The feasibility of microdialysis coupled with liquid chromatography system for direct analysis of neurotransmitters in the rat striatum was investigated. The purposes of the present study were to elucidate the pharmacokinetics of nicotine and evaluate their effects on brain dopaminergic and serotonergic neurotransmission in rat brain. Methods We coupled a microdialysis sampling with on‐line automatic analysis chromatographic system to characterize the pharmacokinetics of both nicotine and cotinine. The electrochemical detection system was employed to determine the striatal dialysates which included dopamine, serotonin and their respective metabolites after i.v. administration of nicotine. Results and Conclusions The results showed nicotine is easy to distribute into the central nervous system. Both drug levels and AUC of nicotine in brain were significantly higher than those in blood. On the other hand, levels of dopamine and serotonin had no significant change compared to baseline after nicotine administration. DOPAC are elevated than baseline in about 100 min interval. Concentrations of both HVA and 5‐HIAA were consistently higher than baseline levels. The results showed nicotine have significant impacts on both dopaminergic and serotonergic neurotransmission in rat brain. Clinical Pharmacology & Therapeutics (2005) 77 , P67–P67; doi: 10.1016/j.clpt.2004.12.148