title: Time-course of extracellular nicotine and cotinine levels in rat brain following administration of nicotine: effects of route and ethanol coadministration.
abstract: BACKGROUND
  Nicotine and ethanol are commonly coabused drugs, and nicotine-laced ethanol products are growing in popularity. However, little is known about time-course changes in extracellular nicotine and cotinine levels in rat models of ethanol and nicotine coabuse.
  
  
  OBJECTIVE
  The objective of the present study was to determine the time-course changes in brain levels of nicotine and cotinine following subcutaneous (SC) and intragastric (IG) nicotine administration in alcohol-preferring (P) and Wistar rats.
  
  
  METHODS
  In vivo microdialysis was used to collect dialysate samples from the nucleus accumbens shell (NACsh) for nicotine and cotinine determinations, following SC administration of (-)-nicotine (0.18, 0.35, and 0.70 mg/kg) in female P and Wistar rats or IG administration of (-)-nicotine (0.35 and 0.70 mg/kg) in 15 % (v/v) ethanol or water in female P rats.
  
  
  RESULTS
  SC nicotine produced nicotine and cotinine dialysate levels as high as 51 and 14 ng/ml, respectively. IG administration of 15 % EtOH + 0.70 mg/kg nicotine in P rats resulted in maximal nicotine and cotinine dialysate levels of 19 and 14 ng/ml, respectively, whereas administration of 0.70 mg/kg nicotine in water resulted in maximal nicotine and cotinine levels of 21 and 25 ng/ml, respectively. Nicotine and cotinine levels were detectable within the first 15 and 45 min, respectively, after IG administration.
  
  
  CONCLUSIONS
  Overall, the results of this study suggest that nicotine is rapidly adsorbed and produces relevant extracellular brain concentrations of nicotine and its pharmacologically active metabolite, cotinine. The persisting high brain concentrations of cotinine may contribute to nicotine addiction.
authors.affiliation: Institute of Psychiatric Research, Department of Psychiatry, Indiana University School of Medicine, Indianapolis, IN, 46202-4887, USA.
authors.forename: Simon N
authors.initials: SN
authors.lastname: Katner
authors.forename: Jamie E
authors.initials: JE
authors.lastname: Toalston
authors.forename: Michael P
authors.initials: MP
authors.lastname: Smoker
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Eric A
authors.initials: EA
authors.lastname: Engleman
mesh_terms: D000437:Alcoholism / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000187:drug effects*; D003367:Cotinine / Q000493:pharmacokinetics*; D004195:Disease Models, Animal; D000431:Ethanol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D009538:Nicotine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D009714:Nucleus Accumbens / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D014029:Tobacco Use Disorder / Q000378:metabolism*
chemical_list: D000431:Ethanol; D009538:Nicotine; D003367:Cotinine