Effects of tolcapone on working memory and brain activity in abstinent smokers: a proof-of-concept study.

Autor: Ashare RL; Center for Interdisciplinary Research on Nicotine Addiction, Department of Psychiatry, University of Pennsylvania, Philadelphia, PA 19104, USA. Electronic address: rlashare@mail.med.upenn.edu., Wileyto EP, Ruparel K, Goelz PM, Hopson RD, Valdez JN, Gur RC, Loughead J, Lerman C
Jazyk: angličtina
Zdroj: Drug and alcohol dependence [Drug Alcohol Depend] 2013 Dec 15; Vol. 133 (3), pp. 852-6. Date of Electronic Publication: 2013 Sep 14.
DOI: 10.1016/j.drugalcdep.2013.09.003
Abstrakt: Background: Dopamine levels in the prefrontal cortex (PFC) are thought to play an important role in cognitive function and nicotine dependence. The catechol-O-methyltransferase (COMT) inhibitor tolcapone, an FDA-approved treatment for Parkinson's disease, increases prefrontal dopamine levels, with cognitive benefits that may vary by COMT genotype. We tested whether tolcapone alters working memory-related brain activity and performance in abstinent smokers.
Methods: In this double-blind crossover study, 20 smokers completed 8 days of treatment with tolcapone and placebo. In both medication periods, smokers completed blood oxygen level-dependent (BOLD) fMRI scans while performing a working memory N-back task after 24h of abstinence. Smokers were genotyped prospectively for the COMT val(158)met polymorphism for exploratory analysis.
Results: Compared to placebo, tolcapone modestly improved accuracy (p=0.017) and enhanced suppression of activation in the ventromedial prefrontal cortex (vmPFC) (p=0.002). There were no effects of medication in other a priori regions of interest (dorsolateral PFC, dorsal cingulate/medial prefrontal cortex, or posterior cingulate cortex). Exploratory analyses suggested that tolcapone led to a decrease in BOLD signal in several regions among smokers with val/val genotypes, but increased or remained unchanged among met allele carriers. Tolcapone did not attenuate craving, mood, or withdrawal symptoms compared to placebo.
Conclusions: Data from this proof-of-concept study do not provide strong support for further evaluation of COMT inhibitors as smoking cessation aids.
(Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
Databáze: MEDLINE
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