title: Plasma nicotine and cotinine levels following intravenous nicotine self-administration in rats.
abstract: BACKGROUND
  The route of nicotine administration between animal models and humans is very different and further investigation by determining levels of nicotine entering into the circulatory system is warranted.
  
  
  OBJECTIVE
  The present study addresses the validity of the rat self-administration procedure by comparing plasma levels of nicotine in the rat with levels reported in smokers following cigarette consumption.
  
  
  METHODS
  Plasma levels of nicotine and its metabolite cotinine were measured in 17 rats following intravenous self-administration of a range of nicotine doses (0.015. 0.03 and 0.06 mg/kg per infusion).
  
  
  RESULTS
  The two larger unit doses supported reliable self-administration behaviour with no overall difference in the patterns of nicotine intake. However, the total nicotine intake over the 2-h session was related to unit dose and this correlated highly with nicotine and cotinine levels measured in blood collected from the tail vein. On average, cotinine levels (50-200 ng/ml) were approximately 2-fold higher than nicotine levels (40-120 ng/ml) in plasma. Following an extinction test for one session in which saline was substituted for nicotine, no change in behaviour was observed in the two groups, while plasma levels of nicotine and cotinine dropped to nominal levels.
  
  
  CONCLUSIONS
  The concentrations of nicotine attained following nicotine self-administration appear to be similar to levels reported in smokers after cigarette consumption, providing further validation of this procedure as an animal model of nicotine dependence.
authors.affiliation: Section of Behavioural Pharmacology, Institute of Psychiatry, DeCrespigny Park, London, UK. Spjumos@iop.bpmf.ac.uk
authors.forename: M
authors.initials: M
authors.lastname: Shoaib
authors.forename: I P
authors.initials: IP
authors.lastname: Stolerman
mesh_terms: D000818:Animals; D016739:Behavior, Addictive / Q000097:blood*; D003367:Cotinine / Q000097:blood*; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000097:blood*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000097:blood*; D051381:Rats
chemical_list: D018722:Nicotinic Agonists; D009538:Nicotine; D003367:Cotinine