ABSTRACT
Title
Effect of the selective CRF-1 receptor antagonist R121919 in an animal model of binge eating
Authors
MV Micioni Di B
School of Pharmacy, Pharmacology Unit, University of Camerino, 62032 Camerino (MC), Italy
School of Pharmacy, Pharmacology Unit, University of Camerino, 62032 Camerino (MC), Italy
Abstract
Episodes of binge eating (BE) in humans are characterized by compulsive, non-homeostatic consumption of an unusually large quantity of highly palatable food (HPF) in a short period of time. Considerable evidence suggests that BE may be caused by a unique interaction between dieting and stress.The present study evaluated the effect of the corticotrophin releasing factor 1 receptor (CRF-1R) antagonist R121919 in female rats, in which BE for HPF was evoked by stress and repeated food restrictions [1]. The model employs female rats in relation to the higher prevalence of binge eating disorders in women than in men.
Four groups of female Sprague-Dawley rats were used: NR+NS was normally fed and not stressed on the test day (d25); NR+S was fed as NR+NS and stressed on d25; R+NS was exposed to 3 cycles of yo-yo dieting (8-day cycles of food restriction/refeeding (4d 66% of the standard chow food intake, 4d food ad libitum) but not stressed; R+S was fed as R+NS and stressed on d25. All groups were fed HPF for 2 h on day 5-6 and 13-14. Stress was induced by preventing access to HPF for 15 min, while rats were able to see and smell it. After the stressful procedure the rats had free access to HPF and standard chow. R121919 was injected subcutaneously 1 h before access to HPF.
BE was selectively observed in R+S, that showed a marked increase in HPF intake in comparison to NR+NS. Intake of standard chow pellets was not significantly modified. HPF intake in R+NS and NR+S was not significantly different from that of NR+NS. R121919 (10-20 mg/kg) significantly reduced HPF intake in R+S, but had no effect in the other 3 groups.
After the stressful procedure, rats showed increased serum corticosterone (CORT) levels. To asses whether CORT is involved in the BE response, R+S and NR+NS were treated with metyrapone, a CORT synthesis inhibitor at the doses of 50 and 100 mg/kg. It failed to prevent BE. Lastly, CORT injection (2.5 and 10 mg/kg) did not induce BE in R+NS, in comparison to NR+NS.
These findings suggest that CRF-1R mechanisms are involved in the BE response following stress and food restrictions; this effect is likely related to its extrahypothalamic functions rather than to its regulatory role in HPA axis activity.
[1] Cifani et al. (2009) Psychopharmacology 204:113-25
Four groups of female Sprague-Dawley rats were used: NR+NS was normally fed and not stressed on the test day (d25); NR+S was fed as NR+NS and stressed on d25; R+NS was exposed to 3 cycles of yo-yo dieting (8-day cycles of food restriction/refeeding (4d 66% of the standard chow food intake, 4d food ad libitum) but not stressed; R+S was fed as R+NS and stressed on d25. All groups were fed HPF for 2 h on day 5-6 and 13-14. Stress was induced by preventing access to HPF for 15 min, while rats were able to see and smell it. After the stressful procedure the rats had free access to HPF and standard chow. R121919 was injected subcutaneously 1 h before access to HPF.
BE was selectively observed in R+S, that showed a marked increase in HPF intake in comparison to NR+NS. Intake of standard chow pellets was not significantly modified. HPF intake in R+NS and NR+S was not significantly different from that of NR+NS. R121919 (10-20 mg/kg) significantly reduced HPF intake in R+S, but had no effect in the other 3 groups.
After the stressful procedure, rats showed increased serum corticosterone (CORT) levels. To asses whether CORT is involved in the BE response, R+S and NR+NS were treated with metyrapone, a CORT synthesis inhibitor at the doses of 50 and 100 mg/kg. It failed to prevent BE. Lastly, CORT injection (2.5 and 10 mg/kg) did not induce BE in R+NS, in comparison to NR+NS.
These findings suggest that CRF-1R mechanisms are involved in the BE response following stress and food restrictions; this effect is likely related to its extrahypothalamic functions rather than to its regulatory role in HPA axis activity.
[1] Cifani et al. (2009) Psychopharmacology 204:113-25