The study investigates the effects of leptin on food intake and energy balance in normal rats, building on previous findings from leptin-deficient mice. Intracerebroventricular (icv) administration of leptin (3.5 μg) reduced food intake by 50% at 1 hour and 42% at 4 hours compared to vehicle-treated controls. In situ hybridization revealed that icv leptin administration during a 40-hour fast decreased neuropeptide Y (NPY) mRNA levels in the arcuate nucleus and increased corticotrophin-releasing hormone (CRH) mRNA levels in the paraventricular nucleus. Leptin receptor mRNA was concentrated in the arcuate nucleus and other hypothalamic nuclei involved in energy balance. These findings suggest that leptin's action in the hypothalamus involves altering the expression of key neuropeptide genes, potentially mediating its effects on food intake and energy balance. The study also highlights the importance of normal leptin receptor function for leptin's effects on hypothalamic gene expression.The study investigates the effects of leptin on food intake and energy balance in normal rats, building on previous findings from leptin-deficient mice. Intracerebroventricular (icv) administration of leptin (3.5 μg) reduced food intake by 50% at 1 hour and 42% at 4 hours compared to vehicle-treated controls. In situ hybridization revealed that icv leptin administration during a 40-hour fast decreased neuropeptide Y (NPY) mRNA levels in the arcuate nucleus and increased corticotrophin-releasing hormone (CRH) mRNA levels in the paraventricular nucleus. Leptin receptor mRNA was concentrated in the arcuate nucleus and other hypothalamic nuclei involved in energy balance. These findings suggest that leptin's action in the hypothalamus involves altering the expression of key neuropeptide genes, potentially mediating its effects on food intake and energy balance. The study also highlights the importance of normal leptin receptor function for leptin's effects on hypothalamic gene expression.