CRF1 and 2 antagonizing astressins(The Salk Institute for Biological Studies)

The present study aimed to assess the probable impact of the central histaminergic and melanocortin systems on leptin-induced hypophagia in neonatal layer chickens. In experiment 1, the chickens received intracerebroventricular (ICV) injections of the control solution, 250 nmol of α-FMH, 10 µg of leptin, and α-FMH+leptin. Experimental groups 2-8 were injected the same as experiment 1. Nonetheless, the chickens in experiments 2-8 received ICV injections of 300 nmol of chlorpheniramine (H₁ receptor antagonist), 82 nmol of famotidine (H₂ receptor antagonist), 300 nmol of thioperamide (H₃ receptor antagonist), 0.5 nmol of SHU9119 (M₃/M₄ receptors antagonist), 0.5 nmol of MCL0020 (M₄ receptor antagonist), 30 µg of astressin-B (CRF₁/ CRF₂ receptors antagonist), and 30 µg of astressin2-B (CRF₂ receptor antagonist), instead of α-FMH, respectively. Food was provided for the birds immediately following the injection, and 30, 60, and 120 min after the injection, cumulative food intake (g) was measured. The findings pointed out that the ICV injection of leptin diminished food intake in neonatal chickens (P<0.05). The co-administration of M₃/M₄ receptor antagonist+leptin significantly decreased the hypophagic effect of leptin (P<0.05). A significant decrease was also detected in the hypophagic effect of leptin following the co-administration of the M₄ receptor antagonist and leptin (P<0.05). Moreover, the co-injection of the antagonists of CRF₁/CRF₂ receptors and leptin significantly mitigated the hypophagic effect of leptin (P<0.05). The co-injection of CRF₂ receptor antagonist and leptin led to a decrease in the hypophagic effect of leptin. As evidenced by the results of the current study the hypophagic effect of leptin is mediated by the receptors of H₁, H₃, M₃/M₄, and CRF₁/CRF₂ in neonatal layer chicken.

The aim of the present study was to investigate the participation of corticotropin-releasing factor (CRF) receptors (CRF1 and CRF2) in the alterations of the dorsal and ventral striatal dopamine release and the vertical and horizontal locomotor activity observed in rats following chronic nicotine treatment and consequent acute withdrawal. In this purpose, male Wistar rats were exposed to repeated intraperitoneal (ip) injection with nicotine or saline solution for 7 days. On the 8th day or the 9th day the rats were injected intracerebroventricularly (icv) with selective CRF1 antagonist antalarmin or selective CRF2 antagonist astressin_2B or saline solution. Thirty minutes after the icv injection the changes of the horizontal and vertical locomotor activity were recorded in an in vivo conducta system. Immediately after the behavioral recordings the changes of the dorsal and ventral striatal dopamine release were determined in an in vitro superfusion system. On the 8th day, the horizontal and vertical locomotor activities and the dorsal and ventral striatal dopamine releases increased significantly in nicotine-treated rats, compared to the saline-treated ones. On the 9th day, the horizontal locomotor activity and the dorsal striatal dopamine release increased significantly, whereas the vertical locomotor activity and the ventral striatal dopamine release decreased significantly in nicotine-treated rats, compared to the saline-treated ones. All the changes observed were attenuated significantly by antalarmin, but not astressin_2B. The present study demonstrates that the changes of striatal dopamine release and locomotor activity observed following chronic nicotine treatment and consequent acute withdrawal are mediated by CRF1, but not CRF2, receptor.