Nicotine normalizes event related potentials in COMT-Val-tg mice and increases gamma and theta spectral density.
Regulation of dopamine neurotransmission is essential for cognitive processes. In humans and rodents, the relationship between dopamine signaling and cognitive performance is described as a dose-dependent, inverted-U curve whereby excess or insufficiency of dopamine in prefrontal cortex has detrimental effects. Previous studies have indicated that prefrontal dopamine levels are associated with genetic variation in catechol-O-methyltransferase (COMT), a regulatory enzyme that controls dopamine availability. Furthermore, smokers who carry the high-activity COMT-Val allele are more prone to cognitive deficits and have an increased risk of smoking relapse. The present study employed transgenic mice expressing the human COMT-Val variant to determine the effects of the high-activity COMT allele on electrophysiological markers, including the P20, N40, and P80 components of the auditory event-related potential, as well as baseline and auditory event-related power and phase-synchrony in theta and gamma ranges. We also examined the effects of nicotine on these measures to investigate the potential effects of smoking on COMT-mediated electrophysiological activity. COMT-Val-tg mice displayed increased N40 latency and decreased P80 amplitude as well as reduced baseline theta and gamma power. Nicotine increased P20 and P80 amplitudes, decreased N40 amplitude, increased P20 and N40 latencies, and reduced P80 latency. Nicotine also increased the event-related power and phase synchrony, yielding an increase in signal-to-noise ratio across theta and gamma ranges. COMT activity specifically alters long-latency components of the event-related response. Nicotine restored normal event-related activity among COMT-Val-tg mice, suggesting one mechanism through which nicotine may normalize cognitive function among people with the high-activity allele.
ranslational Neuroscience Program, Department of Psychiatry, University of Pennsylvania, PA, USA.
Yufei A
YA
Cao
Robert E
RE
Featherstone
Michael J
MJ
Gandal
Yuling
Y
Liang
Catherine
C
Jutzeler
John
J
Saunders
Valerie
V
Tatard-Leitman
Jingshan
J
Chen
Daniel R
DR
Weinberger
Caryn
C
Lerman
Steven J
SJ
Siegel
D000483:Alleles; D000818:Animals; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003071:Cognition / Q000502:physiology; D004298:Dopamine / Q000378:metabolism*; D004569:Electroencephalography; D005071:Evoked Potentials / Q000187:drug effects*; D005260:Female; D005838:Genotype; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000201:enzymology; D013826:Theta Rhythm / Q000187:drug effects*
D018722:Nicotinic Agonists; D009538:Nicotine; D002394:Catechol O-Methyltransferase; D004298:Dopamine