Related Experiment Video
Updated: Jun 20, 2026

The 5-Choice Serial Reaction Time Task: A Task of Attention and Impulse Control for Rodents
Published on: August 10, 2014
Tolcapone effects on gating, working memory, and mood interact with the synonymous catechol-O-methyltransferase
Panos Roussos1, Stella G Giakoumaki, Panos Bitsios
1Department of Psychiatry and Behavioral Sciences, University of Crete, Greece. roussosp@edu.med.uoc.gr
Background:
The functional catechol-O-methyltransferase (COMT) valine158methionine (val158met) polymorphism determines prepulse inhibition (PPI) levels and working memory performance and the effects of tolcapone on these functions. Here, we explored the effects of the synonymous COMT rs4818 C/G polymorphism and tolcapone on PPI and working memory.
Methods:
Thirteen G/G (low prefrontal cortex [PFC] dopamine [DA]) and 12 C/C (high PFC DA) healthy male subjects entered and completed the study. Subjects participated in two weekly sessions associated with either acute oral tolcapone (200 mg) or placebo according to a balanced, crossover, double-blind design. Prepulse inhibition was assessed with 5 dB and 15 dB above background prepulses at 30-msec, 60-msec, and 120-msec intervals. Subjective mood and working memory performance (n-back and letter-number sequencing) were also assessed.
Results:
Prepulse inhibition was lower and reaction time in the n-back was slower in the G/G compared with the C/C group in the placebo condition. Tolcapone increased PPI and improved performance in both working memory tasks in the G/G group only. Baseline startle was greater in the C/C group and was not affected by tolcapone. Mood profile was worse in the C/C group and tended to deteriorate with tolcapone. Status of val158met alone could not explain these results.
Conclusions:
Catechol-O-methyltransferase haplotype analyses are essential in future research. Prepulse inhibition and working memory may both relate to PFC DA levels according to an inverted U-shaped curve function. Tolcapone could be potentially useful in the treatment of conditions with deficient sensorimotor gating and working memory such as schizophrenia and prodromal states but only in a genotype-specific manner.
Related Concept Videos
Pharmacogenetic Phenotypes: Alterations in Pharmacokinetics, Drug Targets and Biologic Milieu
Drugs Affecting Neurotransmitter Synthesis
Drugs Affecting Neurotransmitter Release or Uptake
Pharmacogenetics of Phase II Enzymes: N-acetyltransferase, Thiopurine S-methyltransferase, UDP-glucuronosyltransferase
Pharmacogenetics of Drug Targets: β₂-Adrenergic Receptors, Apo E, Thymidylate Synthase
Human Genetics
The complex relationship between genetics and psychology is observable through common biological components such...
