A preliminary study of the effects of cigarette smoking on prepulse inhibition in schizophrenia: involvement of nicotinic receptor mechanisms.
BACKGROUND
Schizophrenics exhibit deficits in prepulse inhibition (PPI) of the startle response, and have high rates of cigarette smoking. We evaluated the effects of cigarette smoking on PPI deficits in schizophrenia, and the role of nicotinic acetylcholine receptors (nAChRs) in mediating cigarette smoking-related PPI enhancement.


METHODS
PPI was assessed at baseline, after overnight abstinence, and after smoking reinstatement during three separate test weeks in nicotine-dependent schizophrenia (n=15) and control (n=14) smokers pre-treated with the nAChR antagonist mecamylamine (MEC; 0.0, 5.0 or 10.0 mg/day).


RESULTS
PPI was comparable between schizophrenia and control smokers after ad lib cigarette smoking. Overnight smoking abstinence significantly reduced PPI, while smoking reinstatement reversed abstinence-induced worsening of PPI deficits in schizophrenia. However, acute abstinence and reinstatement did not alter PPI in controls. PPI enhancement by smoking reinstatement in schizophrenia was dose-dependently blocked by MEC, whereas MEC had no effect on PPI in control smokers.


CONCLUSIONS
These results suggest that: 1) Non-deprived smokers with schizophrenia have comparable levels of PPI to non-deprived smoking controls; 2) In schizophrenia, PPI is impaired by smoking abstinence and improved by acute smoking reinstatement, and; 3) enhancement of PPI by cigarette smoking in schizophrenia is mediated by stimulation of central nAChRs. Our findings may contribute to understanding the increased vulnerability to nicotine dependence in schizophrenia, with implications for treatment of PPI deficits in this disorder.
George
Tony P
TP
Program for Research in Smokers with Mental Illness (PRISM), Department of Psychiatry, Yale University School of Medicine, Substance Abuse Center, Connecticut Mental Health Center, New Haven, CT 06519, USA. tony.george@utoronto.ca
Termine
Angelo
A
Sacco
Kristi A
KA
Allen
Taryn M
TM
Reutenauer
Erin
E
Vessicchio
Jennifer C
JC
Duncan
Erica J
EJ
D000110:Acetylcholinesterase / Q000378:metabolism; D000328:Adult; D004311:Double-Blind Method; D005260:Female; D005731:Ganglionic Stimulants / Q000008:administration & dosage / Q000494:pharmacology*; D006185:Habituation, Psychophysiologic / Q000187:drug effects; D006801:Humans; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects*; D009538:Nicotine / Q000008:administration & dosage / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D018733:Nicotinic Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects*; D012559:Schizophrenia / Q000453:epidemiology / Q000503:physiopathology*; D012907:Smoking / Q000453:epidemiology; D011795:Surveys and Questionnaires
D005731:Ganglionic Stimulants; D018733:Nicotinic Antagonists; D011978:Receptors, Nicotinic; D008464:Mecamylamine; D009538:Nicotine; D000110:Acetylcholinesterase