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Titolo:
SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats
Autore:
Rodgers, RJ; Halford, JCG; de Souza, RLN; de Souza, ALC; Piper, DC; Arch, JRS; Upton, N; Porter, RA; Johns, A; Blundell, JE;
Indirizzi:
Univ Leeds, Sch Psychol, Leeds LS2 9JT, W Yorkshire, England Univ Leeds Leeds W Yorkshire England LS2 9JT S2 9JT, W Yorkshire, England Univ Liverpool, Dept Psychol, Liverpool L69 7NZ, Merseyside, England Univ Liverpool Liverpool Merseyside England L69 7NZ , Merseyside, England SmithKline Beecham Pharmaceut, Harlow CM19 5AD, Essex, England SmithKline Beecham Pharmaceut Harlow Essex England CM19 5AD ssex, England
Titolo Testata:
EUROPEAN JOURNAL OF NEUROSCIENCE
fascicolo: 7, volume: 13, anno: 2001,
pagine: 1444 - 1452
SICI:
0953-816X(200104)13:7<1444:SASORA>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
LATERAL HYPOTHALAMIC AREA; GENETICALLY-OBESE MICE; FOOD-INTAKE; NEUROPEPTIDE-Y; GENE-EXPRESSION; PREPRO-OREXIN; HYPOCRETIN OREXIN; FEEDING-BEHAVIOR; DOWN-REGULATION; MESSENGER-RNA;
Keywords:
appetite; behavioural satiety sequence; food intake; microstructural analysis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
49
Recensione:
Indirizzi per estratti:
Indirizzo: Rodgers, RJ Univ Leeds, Sch Psychol, Leeds LS2 9JT, W Yorkshire, England Univ Leeds Leeds W Yorkshire England LS2 9JT rkshire, England
Citazione:
R.J. Rodgers et al., "SB-334867, a selective orexin-1 receptor antagonist, enhances behavioural satiety and blocks the hyperphagic effect of orexin-A in rats", EUR J NEURO, 13(7), 2001, pp. 1444-1452

Abstract

Intracerebroventricular (i.c.v.) administration of the novel hypothalamic neuropeptide orexin-A stimulates food intake in rats, and delays the onset of behavioural satiety (i.e. the natural transition from feeding to resting). Furthermore, preliminary findings with the selective orexin-1 receptor antagonist, SB-334867, suggest that orexin-A regulation of food intake is mediated via the orexin-1 receptor. At present, however, little is known about either the intrinsic effects of SB-334867 on the normal structure of feeding behaviour, or its effects upon orexin-A-induced behavioural change. In the present study, we have employed a continuous monitoring technique to characterize the effects of SB-334867 (3-30 mg/kg, i.p.) on the microstructure of rat behaviour during a 1-h test with palatable wet mash. Administered alone, SB-334867 (30 mg/kg, but not lower doses) significantly reduced foodintake and most active behaviours (eating, grooming, sniffing, locomotion and rearing), while increasing resting. Although suggestive of a behaviourally nonselective (i.e. sedative) action, the structure of feeding behaviourwas well-preserved at this dose level, with the reduction in behavioural output clearly attributable to an earlier onset of behavioural satiety. As previously reported, orexin-A (10 mug per rat i.c.v.) stimulated food intake, increased grooming and delayed the onset of behavioural satiety. Pretreatment with SB-334867 dose-dependently blocked these effects of orexin-A, with significant antagonism evident at dose levels (3-10 mg/kg) below those required to produce intrinsic behavioural effects under present test conditions. Together, these findings strongly support the view that orexin-A is involved in the regulation of feeding patterns and that this influence is mediated through the orexin-1 receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 06/04/20 alle ore 00:04:07