TY - JOUR
T1 - 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
AU - Detrait, Eric R.
AU - Carr, Greg V.
AU - Weinberger, Daniel R.
AU - Lamberty, Yves
N1 - Publisher Copyright:
© Copyright 2016 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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.
AB - 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.
KW - Novel Object Recognition
KW - catechol-O-methyl transferase
KW - cognitive enhancers
KW - dopamine
KW - entacapone
KW - mouse
KW - rat
KW - tolcapone
UR - http://www.scopus.com/inward/record.url?scp=84959209975&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84959209975&partnerID=8YFLogxK
U2 - 10.1097/FBP.0000000000000208
DO - 10.1097/FBP.0000000000000208
M3 - Article
C2 - 26919286
AN - SCOPUS:84959209975
SN - 0955-8810
VL - 27
SP - 415
EP - 421
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
IS - 5
ER -