Mouse model predicts effects of smoking and varenicline on event-related potentials in humans.
BACKGROUND
Nicotine alters auditory event-related potentials (ERPs) in rodents and humans and is an effective treatment for smoking cessation. Less is known about the effects of the partial nicotine agonist varenicline on ERPs.


METHODS
We measured the effects of varenicline and nicotine on the mouse P20 and varenicline and smoking on the human P50 in a paired-click task. Eighteen mice were tested following nicotine, varenicline, and their combination. One hundred and fourteen current smokers enrolled in a placebo-controlled within-subject crossover study to test the effects of varenicline during smoking and abstinence. Thirty-two subjects participated in the ERP study, with half receiving placebo first and half varenicline first (VP).


RESULTS
Nicotine and varenicline enhanced mouse P20 amplitude, while nicotine improved P20 habituation by selectively increasing the first-click response. Similar to mice, abstinence reduced P50 habituation relative to smoking by reducing the first-click response. There was no effect of varenicline on P50 amplitude during abstinence across subjects. However, there was a significant effect of medication order on P50 amplitude during abstinence. Subjects in the PV group displayed reduced P50 during abstinence, which was blocked by varenicline. However, subjects in the VP group did not display abstinence-induced P50 reduction.


CONCLUSIONS
Data suggest that smoking improves sensory processing. Varenicline mimics amplitude changes associated with nicotine and smoking but fails to alter habituation. The effect of medication order suggests a possible carryover effect from the previous arm. This study supports the predictive validity of ERPs in mice as a marker of drug effects in human studies.
Rudnick
Noam D
ND
Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA.
Strasser
Andrew A
AA
Phillips
Jennifer M
JM
Jepson
Christopher
C
Patterson
Freda
F
Frey
Joseph M
JM
Turetsky
Bruce I
BI
Lerman
Caryn
C
Siegel
Steven J
SJ
D000328:Adult; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D018592:Cross-Over Studies; D005071:Evoked Potentials / Q000187:drug effects*; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009538:Nicotine / Q000494:pharmacology*; D015990:Placebo Effect; D011810:Quinoxalines / Q000494:pharmacology*; D012907:Smoking / Q000009:adverse effects*; D000068580:Varenicline; D055815:Young Adult
D001552:Benzazepines; D011810:Quinoxalines; D009538:Nicotine; D000068580:Varenicline
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