title: Effects of chronic nicotine, nicotine withdrawal and subsequent nicotine challenges on behavioural inhibition in rats.
abstract: BACKGROUND
  Drug addiction is a chronically relapsing disorder characterised by compulsive drug use and loss of control over drug intake. Although several theories propose impulsivity as a key component of addiction, the precise nature of this relationship remains unclear.
  
  
  OBJECTIVE
  This study aims to investigate the short- and longer-term effects of chronic nicotine administration on behavioural inhibition.
  
  
  METHODS
  Rats were trained on a symmetrically reinforced go/no-go task, following which they were subcutaneously prepared with osmotic minipumps delivering either nicotine (3.16 mg kg(-1) day(-1) (freebase)) or saline for 7 days. Performance was assessed daily during chronic treatment, in early and late abstinence, and in response to acute nicotine challenges following prolonged abstinence.
  
  
  RESULTS
  Chronic nicotine resulted in a transient reduction in inhibitory control. Spontaneous withdrawal was associated with a nicotine abstinence syndrome, the early stages of which were characterised by a significant increase in inhibitory control. This was, however, short-lived with a decrease in inhibition observed in the second week of abstinence. Whilst performance returned to baseline by the end of the third week, acute challenges (0.125, 0.25, 0.5 mg/kg, SC) revealed that nicotine exposure had sensitised animals to the disinhibitory effects of the compound.
  
  
  CONCLUSIONS
  Drug-induced loss of inhibitory control may be critically involved both in the initial and later stages of addiction. Neuroadaptations occurring during chronic exposure to and/or withdrawal from nicotine render animals more sensitive to the disinhibitory effects of the drug. Longer-term changes in behaviour may play an important role in the increased susceptibility to relapse in those with a history of nicotine abuse.
authors: Behavioural Neuroscience Laboratory, Institute of Psychological Sciences, University of Leeds, Leeds, LS2 9JT, UK. z.kolokotroni@leedsmet.ac.uk
authors: K Z
authors: KZ
authors: Kolokotroni
authors: R J
authors: RJ
authors: Rodgers
authors: A A
authors: AA
authors: Harrison
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D004192:Discrimination, Psychological / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D015918:Infusion Pumps, Implantable / Q000523:psychology; D007266:Inhibition, Psychological; D008297:Male; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D051381:Rats; D013375:Substance Withdrawal Syndrome / Q000523:psychology*
chemical_list: D009538:Nicotine