Brain catechol-O-methyltransferase (COMT) inhibition by tolcapone counteracts recognition memory deficits in normal and chronic phencyclidine-treated rats and in COMT-Val transgenic mice

Eric R. Detrait, Greg V. Carr, Daniel R. Weinberger, Yves Lamberty

Research output: Contribution to journalArticle

Abstract

The critical involvement of dopamine in cognitive processes has been well established, suggesting that therapies targeting dopamine metabolism may alleviate cognitive dysfunction. Catechol-O-methyl transferase (COMT) is a catecholamine-degrading enzyme, the substrates of which include dopamine, epinephrine, and norepinephrine. The present work illustrates the potential therapeutic efficacy of COMT inhibition in alleviating cognitive impairment. A brainpenetrant COMT inhibitor, tolcapone, was tested in normal and phencyclidine-treated rats and COMT-Val transgenic mice. In a novel object recognition procedure, tolcapone counteracted a 24-h-dependent forgetting of a familiar object as well as phencyclidine-induced recognition deficits in the rats at doses ranging from 7.5 to 30 mg/kg. In contrast, entacapone, a COMT inhibitor that does not readily cross the blood-brain barrier, failed to show efficacy at doses up to 30 mg/kg. Tolcapone at a dose of 30 mg/kg also improved novel object recognition performance in transgenic mice, which showed clear recognition deficits. Complementing earlier studies, our results indicate that central inhibition of COMT positively impacts recognition memory processes and might constitute an appealing treatment for cognitive dysfunction related to neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)415-421
Number of pages7
JournalBehavioural Pharmacology
Volume27
Issue number5
DOIs
StatePublished - Aug 1 2016

Keywords

  • Novel Object Recognition
  • catechol-O-methyl transferase
  • cognitive enhancers
  • dopamine
  • entacapone
  • mouse
  • rat
  • tolcapone

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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