title: Nicotine modulates alcohol-seeking and relapse by alcohol-preferring (P) rats in a time-dependent manner.
abstract: BACKGROUND
  Alcohol is frequently co-abused with smoking. In humans, nicotine use can increase alcohol craving and consumption. The objectives of the current study were to assess the acute effects of nicotine on alcohol seeking and relapse at 2 different time points.
  
  
  METHODS
  Adult female alcohol-preferring (P) rats were trained in 2-lever operant chambers to self-administer 15% ethanol (EtOH) (v/v) and water on a concurrent fixed-ratio 5-fixed-ratio 1 (FR5-FR1) schedule of reinforcement in daily 1-hour sessions. Following 10 weeks of daily 1-hour sessions, rats underwent 7 extinction sessions, followed by 2 weeks in their home cages. Rats were then returned to the operant chambers without EtOH or water being present for 4 sessions (Pavlovian Spontaneous Recovery [PSR]). Rats were then given a week in their home cage before being returned to the operant chambers with access to EtOH and water (relapse). Nicotine (0, 0.1, 0.3, or 1.0 mg/kg) was injected subcutaneously immediately or 4 hours prior to PSR or relapse testing.
  
  
  RESULTS
  Injections of nicotine immediately prior to testing reduced (5 to 10 responses PSR; 50 to 60 responses relapse), whereas injections of nicotine 4 hours prior to testing increased (up to 150 responses for PSR; up to 400 responses for relapse with 1.0 mg/kg dose) responses on the EtOH lever during PSR and relapse tests.
  
  
  CONCLUSIONS
  The results of this study demonstrate that acute effects of nicotine on EtOH-seeking and relapse behaviors may be time dependent, with the immediate effects being a result of nicotine possibly acting as a substitute for EtOH, whereas with a delay of 4 hours, priming effects of nicotine alterations in nicotinic receptors, and/or the effects of nicotine's metabolites (i.e., cotinine and nornicotine) may enhance the expression of EtOH-seeking and relapse behaviors.
authors.affiliation: Department of Psychiatry, Institute of Psychiatric Research, Indiana University School of Medicine, Indiana University-Purdue University at Indianapolis, 46202-4887, USA. shhauser@iupui.edu
authors.forename: Sheketha R
authors.initials: SR
authors.lastname: Hauser
authors.forename: Bruk
authors.initials: B
authors.lastname: Getachew
authors.forename: Scott M
authors.initials: SM
authors.lastname: Oster
authors.forename: Ronnie
authors.initials: R
authors.lastname: Dhaher
authors.forename: Zheng-Ming
authors.initials: ZM
authors.lastname: Ding
authors.forename: Richard L
authors.initials: RL
authors.lastname: Bell
authors.forename: William J
authors.initials: WJ
authors.lastname: McBride
authors.forename: Zachary A
authors.initials: ZA
authors.lastname: Rodd
mesh_terms: D000428:Alcohol Drinking / Q000188:drug therapy* / Q000235:genetics*; D000818:Animals; D016739:Behavior, Addictive / Q000188:drug therapy* / Q000235:genetics*; D003216:Conditioning, Operant / Q000187:drug effects / Q000502:physiology; D005260:Female; D009538:Nicotine / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D011930:Reaction Time / Q000187:drug effects* / Q000502:physiology; D055502:Secondary Prevention; D013045:Species Specificity
chemical_list: D009538:Nicotine