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Titolo:
TOLCAPONE - A POTENTIAL NEW ANTIDEPRESSANT DETECTED IN A NOVEL ANIMAL-MODEL OF DEPRESSION
Autore:
MOREAU JL; BORGULYA J; JENCK F; MARTIN JR;
Indirizzi:
F HOFFMANN LA ROCHE & CO LTD,PRECLIN CNS RES,DIV PHARMA CH-4002 BASELSWITZERLAND
Titolo Testata:
Behavioural pharmacology
fascicolo: 3, volume: 5, anno: 1994,
pagine: 344 - 350
SICI:
0955-8810(1994)5:3<344:T-APNA>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
STRESS-INDUCED ANHEDONIA; CHRONIC MILD STRESS; TIME-DEPENDENT RESPONSES; MESOLIMBIC DOPAMINE; PARKINSONS-DISEASE; SYSTEM; SUBSENSITIVITY; ACTIVATION; PREFERENCE; INHIBITOR;
Keywords:
ANHEDONIA; CHRONIC MILD STRESS; COMT INHIBITOR; DEPRESSION; MODEL; SELF-STIMULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
36
Recensione:
Indirizzi per estratti:
Citazione:
J.L. Moreau et al., "TOLCAPONE - A POTENTIAL NEW ANTIDEPRESSANT DETECTED IN A NOVEL ANIMAL-MODEL OF DEPRESSION", Behavioural pharmacology, 5(3), 1994, pp. 344-350

Abstract

The potential antidepressant properties of tolcapone, a new catechol-O-methyl transferase (COMT) inhibitor, were investigated in a novel animal model of depression. Chronic mild stress (CMS)-induced anhedonia in rats is recognized as a model of depression with predictive and etiological validity. Here, the effects of CMS on the hedonic state of animals were assessed using a self-stimulation paradigm in which rats self-activate the ventral tegmental area. Frequency thresholds for self-stimulation responses were determined prior to, during and after a 19 day period of exposure to a variety of intermittent, unpredictable, mild stressors. In vehicle-treated stressed animals, stimulation threshold was significantly increased after about 12 days, reflecting a gradual development of an ''anhedonic'' state. This anhedonia persisted throughout the stress period and subsequently disappeared over a 10 day period. This stress-induced anhedonic state was not observed in stressed rats concomitantly treated with tolcapone (10 or 30 mg/kg b.i.d.). In non-stressed vehicle- or drug-treated animals, no significant changein self-stimulation threshold was consistently observed. These results suggest that selective, reversible COMT inhibitors such as tolcaponemay offer an innovative approach to the treatment of depression, in addition to their potential therapeutic use in Parkinson's disease.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 23/01/20 alle ore 12:16:40