title: Manipulation of nicotinic acetylcholine receptors differentially affects behavioral inhibition in human subjects with and without disordered baseline impulsivity.
abstract: BACKGROUND
  Evidence for a relationship between cigarette smoking and attention-deficit/hyperactivity disorder (ADHD) has prompted investigations into nicotinic treatments for this disorder. Impulsivity is a hallmark of ADHD and is measured in the laboratory as behavioral inhibition (BI) using the stop signal task (SST). Acute nicotine improves SST performance in adolescents and young adults who have both ADHD and impaired baseline SST performance, raising questions about the role of nicotinic acetylcholine receptor function in BI. The specificity of this effect to those with ADHD, the component processes of the SST affected by nicotine, and the effects of nicotinic antagonism are yet unknown.
  
  
  OBJECTIVE
  This study investigated the effects of both a nicotinic receptor agonist and antagonist on the SST and choice reaction time task (CRT) in highly impulsive (HI) and control (CTRL) subjects.
  
  
  METHODS
  This was a within-subjects, double-blind study of: 7 mg transdermal nicotine, 20 mg oral mecamylamine, and placebo. Subjects were recruited into HI (n = 11) and CTRL (n = 14) groups based on both SST and clinical criteria.
  
  
  RESULTS
  BI was significantly improved by nicotine compared with placebo in the HI group and impaired by mecamylamine in the CTRL group. Go signal reaction time on the SST was improved by nicotine compared with placebo in the CTRL group and was unchanged in both groups on the CRT.
  
  
  CONCLUSIONS
  These findings demonstrate nicotinic modulation of BI in subjects with both normal and disordered baseline performance. The effects on BI are consistent with cholinergic enhancement of signal detection processes and/or modulation of noradrenaline by nicotine.
authors.affiliation: Clinical Neuroscience Research Unit, Department of Psychiatry, University of Vermont, 1 South Prospect Street, Burlington, VT 05401, USA. Alexandra.Potter@uvm.edu
authors.forename: Alexandra S
authors.initials: AS
authors.lastname: Potter
authors.forename: David J
authors.initials: DJ
authors.lastname: Bucci
authors.forename: Paul A
authors.initials: PA
authors.lastname: Newhouse
mesh_terms: D000279:Administration, Cutaneous; D000293:Adolescent; D002755:Choice Behavior / Q000187:drug effects / Q000502:physiology; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007175:Impulsive Behavior / Q000188:drug therapy*; D007266:Inhibition, Psychological; D008297:Male; D008464:Mecamylamine / Q000009:adverse effects / Q000494:pharmacology; D009538:Nicotine / Q000008:administration & dosage / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D018722:Nicotinic Agonists / Q000494:pharmacology; D018733:Nicotinic Antagonists / Q000494:pharmacology; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D011978:Receptors, Nicotinic / Q000502:physiology*; D055815:Young Adult
chemical_list: D018722:Nicotinic Agonists; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine