Effects of butorphanol on feeding and neuropeptide Y in the rat

Butorphanol ([BT] an opioid receptor agonist/antagonist) is different from other opioid agonists in that a single dose of BT can elicit up to 12 g of chow intake in a satiated rat whereas most opioid agonists induce a mild feeding response (2-3 g). Here, we first examined whether the effectiveness of BT to elicit feeding was affected by dose, method of infusion and possible tachyphylaxis following administration. Secondly, we examined whether BT administration influenced hypothalamic NPY gene expression and peptide levels. A single dose administration of BT (4 mg/kg) significantly increased food intake at 2, 3 and 6 h after administration. However following repeated injections of BT at 4 mg/kg, the cumulative long-term intake of BT-treated rats did not differ from that of controls, indicating that the animals compensate for the increased feeding following BT injection by decreased feeding at a later time. An ascending dose schedule of repeated BT injections resulted in additional feeding. NPY gene expression in the ARC was influenced by how much food had been consumed, but not by BT. The amount of food consumed and the level of NPY mRNA were inversely correlated. This is consistent with NPY's role in normal feeding. BT treatment did not affect either NPY or leptin RIA levels. We conclude that the feeding produced by BT is sensitive to dose and dosing paradigm. Further, its mechanism of action does not appear to be mediated by NPY or leptin pathways.