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Anorexia and weight loss in male rats 24h following single dose treatment with orexin-1 receptor antagonist SB-334867
- Source :
- Behavioural Brain Research. 157:331-341
- Publication Year :
- 2005
- Publisher :
- Elsevier BV, 2005.
-
Abstract
- Acute systemic treatment with the selective orexin-1 receptor antagonist SB-334867 (30 mg/kg, i.p.) has been reported not only to inhibit food intake and to accelerate behavioural satiety in rats, but also to produce a significant loss of bodyweight over the 24 h period post-dosing. The present studies were designed to test the hypothesis that the inhibition of weight gain following acute treatment with SB-334867 is due to a persistent anorectic action of the compound. In Experiment 1, the acute effects of SB-334867 (30 mg/kg, i.p.) on food intake and behaviour in a 1 h test with palatable mash were assessed as a function of injection-test interval. Results confirmed that, when administered 30 min prior to testing, SB-334867 significantly suppressed mash intake and accelerated behavioural satiety. More importantly, significant anorexia and behavioural change were also observed when animals were tested 24 h, but not 48 h, post-dosing. As previously reported, all animals treated with the orexin-1 receptor antagonist lost bodyweight over the 24 h period following acute treatment. The generality of these findings was confirmed in Experiment 2, where acute treatment with SB-334867 (30 mg/kg, i.p.) significantly suppressed home cage chow consumption over the 24 h period post-dosing, an effect also accompanied by a significant loss of bodyweight. The results of Experiment 3 showed that, following i.p. administration of 30 mg/kg, SB-334867 has good CNS penetration, reaches peak plasma and brain concentrations at 30 min, and maintains good exposure over 4 h post-dosing. Overall, current data support the hypothesis that a persistent anorectic action contributes to the significant loss of bodyweight observed 24 h following acute dosing with SB-334867. As the compound is virtually undetectable in plasma or brain beyond 8 h post-dosing, and since nothing is known about potentially active metabolites, we consider the possibility that single dose treatment with SB-334867 results in enduring alterations to the orexin-1 receptor and/or downstream signalling pathways.
- Subjects :
- Activity Cycles
Male
Receptors, Neuropeptide
medicine.medical_specialty
Time Factors
medicine.drug_class
Anorexia
Drug Administration Schedule
Receptors, G-Protein-Coupled
Eating
Behavioral Neuroscience
SB-334867
Orexin Receptors
Weight loss
Internal medicine
Appetite Depressants
Weight Loss
medicine
Animals
Urea
Naphthyridines
Analysis of Variance
Benzoxazoles
business.industry
Body Weight
Rats, Inbred Strains
Feeding Behavior
Receptor antagonist
Orexin receptor
Rats
Orexin
Endocrinology
Anorectic
medicine.symptom
business
Weight gain
Injections, Intraperitoneal
Subjects
Details
- ISSN :
- 01664328
- Volume :
- 157
- Database :
- OpenAIRE
- Journal :
- Behavioural Brain Research
- Accession number :
- edsair.doi.dedup.....16f5f34d0c6b5d883e3e425a7d48facc
- Full Text :
- https://doi.org/10.1016/j.bbr.2004.07.012