Abstract
Corticotropin-releasing factor (CRF) has been reported to reduce food intake and body weight, and numerous studies suggest a role for CRF in putative mechanisms for the regulation of body energy. This study investigated the effects of ICV-administered antisense phosphorothioate oligonucleotides, directed against the CRF mRNA, on feeding behavior and body weight in rats. Sixteen male HSD rats were cannulated in the lateral ventricle, and given ad libitum access to tap water and a ground chow diet. Feeding behavior was recorded by computer, and meal patterns were assessed. Rats were given 3 micrograms each of two anti-CRF oligonucleotides (aCRF) or two control oligos in the hour before the onset of the nocturnal cycle for ten consecutive days. Cumulative food intake was assessed at 3, 6, 12 and 24 h after each injection, as well as over the 10-day injection period. Compared to missense controls, rats receiving the antisense oligonucleotides ate significantly more at 6 h (P = 0.01), but not at 3, 12, 24 h, or during the entire 10-day injection period (P > 0.05). There was no effect on body weight change, meal size, or meal interval (P > 0.05). These data indicate that daily administration of anti-CRF oligonucleotides has a signifi...Continue Reading
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