title: A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia.
abstract: BACKGROUND
  Schizophrenia patients display an excessive rate of smoking compared to the general population. Nicotine increases acoustic prepulse inhibition (PPI) in animals as well as healthy humans, suggesting that smoking may provide a way of restoring deficient sensorimotor gating in schizophrenia. No previous study has examined the neural mechanisms of the effect of nicotine on PPI in humans.
  
  
  OBJECTIVE
  To investigate whether nicotine enhances tactile PPI in healthy subjects and patients with schizophrenia employing a double-blind, placebo-controlled, cross-over design and, if so, what are the neural correlates of nicotine-induced modulation of PPI.
  
  
  METHODS
  In experiment 1, 12 healthy smokers, 12 healthy non-smokers and nine smoking schizophrenia patients underwent testing for tactile PPI on two occasions, 14 days apart, once after receiving (subcutaneously) 12 microg/kg body weight of nicotine and once after receiving saline (placebo). In experiment 2, six healthy subjects and five schizophrenia patients of the original sample (all male smokers) underwent functional magnetic resonance imaging (fMRI) under the same drug conditions and the same tactile PPI paradigm as in experiment 1.
  
  
  RESULTS
  Nicotine enhanced PPI in both groups. A comparison of patterns of brain activation on nicotine vs placebo conditions showed increased activation of limbic regions and striatum in both groups after nicotine administration. Subsequent correlational analyses demonstrated that the PPI-enhancing effect of nicotine was related to increased hippocampal activity in both groups.
  
  
  CONCLUSIONS
  Nicotine enhances tactile PPI in both healthy and schizophrenia groups. Our preliminary fMRI findings reveal that this effect is modulated by increased limbic activity.
authors.affiliation: Department of Psychology, P078, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
authors.forename: Peggy
authors.initials: P
authors.lastname: Postma
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Gray
authors.forename: Tonmoy
authors.initials: T
authors.lastname: Sharma
authors.forename: Mark
authors.initials: M
authors.lastname: Geyer
authors.forename: Ravi
authors.initials: R
authors.lastname: Mehrotra
authors.forename: Mrigen
authors.initials: M
authors.lastname: Das
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Zachariah
authors.forename: Melissa
authors.initials: M
authors.lastname: Hines
authors.forename: Steven C R
authors.initials: SC
authors.lastname: Williams
authors.forename: Veena
authors.initials: V
authors.lastname: Kumari
mesh_terms: D000328:Adult; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001288:Attention / Q000187:drug effects* / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000503:physiopathology; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004357:Drug Synergism; D006624:Hippocampus / Q000187:drug effects / Q000503:physiopathology; D006801:Humans; D007089:Image Enhancement; D007091:Image Processing, Computer-Assisted; D007279:Injections, Subcutaneous; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000008:administration & dosage* / Q000009:adverse effects; D010100:Oxygen / Q000097:blood*; D013216:Reflex, Startle / Q000187:drug effects* / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology*; D012565:Schizophrenic Psychology; D012907:Smoking / Q000503:physiopathology* / Q000523:psychology; D014029:Tobacco Use Disorder / Q000503:physiopathology* / Q000523:psychology; D014110:Touch / Q000187:drug effects* / Q000502:physiology
chemical_list: D009538:Nicotine; D010100:Oxygen