کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9406855 | 1290141 | 2005 | 11 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Anorexia and weight loss in male rats 24Â h following single dose treatment with orexin-1 receptor antagonist SB-334867
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب رفتاری
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چکیده انگلیسی
Acute systemic treatment with the selective orexin-1 receptor antagonist SB-334867 (30Â 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 24Â 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 (30Â mg/kg, i.p.) on food intake and behaviour in a 1Â h test with palatable mash were assessed as a function of injection-test interval. Results confirmed that, when administered 30Â 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 24Â h, but not 48Â h, post-dosing. As previously reported, all animals treated with the orexin-1 receptor antagonist lost bodyweight over the 24Â h period following acute treatment. The generality of these findings was confirmed in Experiment 2, where acute treatment with SB-334867 (30Â mg/kg, i.p.) significantly suppressed home cage chow consumption over the 24Â 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 30Â mg/kg, SB-334867 has good CNS penetration, reaches peak plasma and brain concentrations at 30Â min, and maintains good exposure over 4Â h post-dosing. Overall, current data support the hypothesis that a persistent anorectic action contributes to the significant loss of bodyweight observed 24Â h following acute dosing with SB-334867. As the compound is virtually undetectable in plasma or brain beyond 8Â 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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Behavioural Brain Research - Volume 157, Issue 2, 28 February 2005, Pages 331-341
Journal: Behavioural Brain Research - Volume 157, Issue 2, 28 February 2005, Pages 331-341
نویسندگان
Y. Ishii, J.E. Blundell, J.C.G. Halford, N. Upton, R. Porter, A. Johns, P. Jeffrey, S. Summerfield, R.J. Rodgers,