Hypothalamic neuropeptide Y (NPY) and the attenuation of hyperphagia in streptozotocin diabetic rats treated with dopamine D 1/ D 2 agonists

1 Dopamine is an appetite suppressant, while neuropeptide Y (NPY), an appetite stimulant in the brain, is reported to be involved in anorectic action induced by a combined administration of D 1/ D 2 agonists in normal rats. In diabetic rats, however, these factors have not been studied. 2 Rats (including normal, diabetic and insulin‐treated diabetic rats) were given daily injections of saline or D 1/ D 2 agonists for 6 days. Changes in food intake and hypothalamic NPY content of these rats were assessed and compared. 3 The D 1/ D 2 agonist‐induced anorectic responses were altered in diabetic rats compared to normal rats treated similarly. Both the anorectic response on the first day of dosing and the tolerant response on the subsequent days were attenuated. 4 This alteration was independent of the neuroendocrine disturbance on feeding behavior since the basic pattern of food intake during the time course of a 24‐h day/night cycle was similar in normal and diabetic rats; the decrease of food intake following drug treatment was only shown at the initial interval of 0–6 h in both groups of rats. 5 However, this alteration coincided with changes in NPY content following D 1/ D 2 coadministration. The replacement of insulin in diabetic rats could normalize both NPY content and D 1/ D 2 agonist‐induced anorexia. 6 It is demonstrated that the response of D 1/ D 2 agonist‐induced appetite suppression is attenuated in diabetic rats compared to normal rats and that elevated hypothalamic NPY content may contribute to this alteration.British Journal of Pharmacology (2006) 148 , 640–647. doi: 10.1038/sj.bjp.0706754