A behavioural and functional neuroimaging investigation into the effects of nicotine on sensorimotor gating in healthy subjects and persons with schizophrenia.
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.
Postma
Peggy
P
Department of Psychology, P078, Institute of Psychiatry, King's College London, De Crespigny Park, London SE5 8AF, UK.
Gray
Jeffrey A
JA
Sharma
Tonmoy
T
Geyer
Mark
M
Mehrotra
Ravi
R
Das
Mrigen
M
Zachariah
Elizabeth
E
Hines
Melissa
M
Williams
Steven C R
SC
Kumari
Veena
V
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
D009538:Nicotine; D010100:Oxygen