Chronic i.c.v infusion either of a melanocortin agonist or of an antagonist at low doses profoundly modifies energy balance without any other behavioral effects, in rats

We investigated whether the chronic (for 12 days) i.c.v. infusion of a non selective melanocortin agonist (ACTH1-24, 0.5 μg/h) or of a selective melanocortin MC4 receptor antagonist (HS024, 0.25 μg/h), at low doses, influences some behavioral functions (spatial learning, spontaneous motility, anxiety, pain thereshold) and energy balance.During the chronic i.c.v. infusion of either ACTH1-24 or HS024 none of the behavioral functions studied was significantly changed. On the other hand, HS024-infused rats ate much more food (200%) than saline-infused rats and became obese (126% of control body weight).ACTH-infused rats ate less food than controls only during the first day of treatment, while their body weight decreased significantly until the end of the infusion period (90% of control body weight). Moreover ACTH1-24 infusion significantly increased the expression of mRNA UCP1 in the brown adipose tissue and decreased UCP2 mRNA in the liver. These results strengthen the therapeutic potential of melanocortin drugs in the treatment of obesity and anorexia.