title: Cellular nicotinic receptor desensitization correlates with nicotine-induced acute behavioral tolerance in rats.
abstract: BACKGROUND
  Individuals vary in their susceptibility to nicotine addiction. However, there is little evidence that behavioral sensitivity to nicotine is dependent upon the functional state of nicotinic cholinergic receptors (nAChRs).
  
  
  OBJECTIVE
  This study aims to determine the relationship between in vivo behavioral desensitization and in vitro desensitization of nAChR function.
  
  
  METHODS
  Male Sprague-Dawley rats trained to discriminate nicotine were tested for development of acute behavioral tolerance. The rats were injected with nicotine (0.4 mg/kg free base, s.c.), tested for nicotine discrimination for 2 min, then injected with the same dose of nicotine 90, 180, and 270 min after the first injection and tested for nicotine discrimination after each injection. Susceptibility of nAChRs of individual rats to desensitization was assessed by use of the (86)Rb(+) efflux assay using synaptosomes prepared from the "thalamus," which included the hypothalamus and midbrain as well as the thalamic nuclei. To desensitize nAChRs, synaptsosomes were superfused with low concentrations of nicotine (5, 10, 20, and 30 nM) before stimulation of (86)Rb(+) efflux with nicotine (10 muM).
  
  
  RESULTS
  The slopes of the behavioral desensitization were plotted as a function of the decline of nicotine-stimulated (86)Rb(+) efflux after in vitro desensitization. A significant correlation was observed between the in vitro desensitization of thalamic (86)Rb(+) efflux and the extent of behavioral desensitization of individual rats.
  
  
  CONCLUSIONS
  These findings are consistent with the idea that production of acute behavioral tolerance by nicotine is related to its ability to induce nAChR desensitization at the cellular level.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, Richmond, VA 23298-0613, USA. serobins@vcu.edu
authors.forename: Susan E
authors.initials: SE
authors.lastname: Robinson
authors.forename: Robert E
authors.initials: RE
authors.lastname: Vann
authors.forename: Angela F
authors.initials: AF
authors.lastname: Britton
authors.forename: Mary M
authors.initials: MM
authors.lastname: O'Connell
authors.forename: John R
authors.initials: JR
authors.lastname: James
authors.forename: John A
authors.initials: JA
authors.lastname: Rosecrans
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003216:Conditioning, Operant / Q000187:drug effects; D004193:Discrimination Learning / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012414:Rubidium Radioisotopes; D013574:Synaptosomes
chemical_list: D018722:Nicotinic Agonists; D011978:Receptors, Nicotinic; D012414:Rubidium Radioisotopes; D009538:Nicotine