title: Effects of caffeine on persistence and reinstatement of nicotine-seeking behavior in rats: interaction with nicotine-associated cues.
abstract: BACKGROUND
  Caffeine and nicotine are the most commonly co-used psychostimulants. However, it is still unclear whether caffeine exposure enhances nicotine-seeking behavior.
  
  
  OBJECTIVE
  The present study examined the effects of caffeine on nicotine-seeking in rats trained to self-administer nicotine with and without presession administration of caffeine.
  
  
  METHODS
  Male Sprague-Dawley rats were trained to intravenously self-administer nicotine (0.03 mg/kg/infusion, freebase) on a fixed ratio 5 schedule of reinforcement and associate a stimulus cue with each nicotine administration. Five minutes before the sessions, the rats received an intraperitoneal administration of caffeine (5 mg/kg). Extinction tests were conducted under four conditions: presession caffeine administration, response-contingent presentation of nicotine cues, neither condition, or both conditions. Reinstatement tests were conducted after responding was extinguished by withholding presession caffeine, nicotine, and its cues. A separate group of rats trained without presession caffeine exposure was also subjected to the reinstatement tests.
  
  
  RESULTS
  In the rats trained with presession caffeine exposure, continued caffeine administration sustained nicotine-seeking responses and interacted with nicotine cues to significantly delay the extinction of nicotine-seeking behavior. Readministration of caffeine after extinction effectively reinstated nicotine-seeking behavior. In caffeine-naive rats, caffeine administration did not reinstate extinguished nicotine-seeking behavior but significantly potentiated the cue-induced reinstatement of nicotine-seeking.
  
  
  CONCLUSIONS
  These data demonstrate that caffeine administration sustained and reinstated nicotine-seeking behavior, possibly via its acquired discriminative-stimulus properties predictive of nicotine availability. These findings suggest that smokers who attempt to quit may benefit from stopping caffeine consumption.
authors.affiliation: Department of Psychiatry and Human Behavior, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS, 39216, USA. xliu@umc.edu
authors.forename: Xiu
authors.initials: X
authors.lastname: Liu
authors.forename: Courtney
authors.initials: C
authors.lastname: Jernigan
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002110:Caffeine / Q000494:pharmacology*; D000697:Central Nervous System Stimulants / Q000494:pharmacology*; D003216:Conditioning, Operant / Q000187:drug effects; D003463:Cues; D004193:Discrimination Learning / Q000187:drug effects; D005108:Extinction, Psychological / Q000187:drug effects; D007262:Infusions, Intravenous; D007274:Injections, Intraperitoneal; D008297:Male; D009538:Nicotine / Q000008:administration & dosage*; D018722:Nicotinic Agonists / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012054:Reinforcement, Psychology; D012646:Self Administration
chemical_list: D000697:Central Nervous System Stimulants; D018722:Nicotinic Agonists; D002110:Caffeine; D009538:Nicotine