ICV ADMINISTRATION OF ANTI-CORTICOTROPIN-RELEASING FACTOR ANTISENSE OLIGONUCLEOTIDE - EFFECTS ON FEEDING-BEHAVIOR AND BODY-WEIGHT

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 inv estigated the effects of ICV-administered antisense phosphorothioate o ligonucleotides, directed against the CRF mRNA, on feeding behavior an d body weight in rats. Sixteen male HSD rats were cannulated in the la teral ventricle, and given ad libitum access to tap water and a ground chow diet. Feeding behavior was recorded by computer, and meal patter ns were assessed. Rats were given 3 mu g each of two anti-CRF oligonuc leotides (aCRF) or two control oligos in the hour before the onset of the nocturnal cycle for ten consecutive days. Cumulative food intake w as 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 rece iving 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 si ze, or meal interval (P > 0.05). These data indicate that daily admini stration of anti-CRF oligonucleotides has a significant short-term sti mulatory effect on feeding behavior, but does not have a long-term eff ect on feeding or body weight gain.