Hypothalamic neuropeptide Y (NPY) and the attenuation of hyperphagia in streptozotocin diabetic rats treated with dopamine D1/D2 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 D1/D2 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 D1/D2 agonists for 6 days. Changes in food intake and hypothalamic NPY content of these rats were assessed and compared. 3. The D1/D2 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 D1/D2 coadministration. The replacement of insulin in diabetic rats could normalize both NPY content and D1/D2 agonist-induced anorexia. 6. It is demonstrated that the response of D1/D2 agonist-induced appetite suppression is attenuated in diabetic rats compared to normal rats and that elevated hypothalamic NPY content may contribute to this alteration.
Kuo
Dong-Yih
DY
Department of Physiology, Chung Shan Medical University, Taichung City, Taiwan 40201, ROC. dykuo@csmu.edu.tw
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000008:administration & dosage / Q000627:therapeutic use; D000818:Animals; D001067:Appetite Depressants / Q000627:therapeutic use; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy*; D018491:Dopamine Agonists / Q000008:administration & dosage / Q000627:therapeutic use*; D004333:Drug Administration Routes; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D005247:Feeding Behavior / Q000187:drug effects; D020249:Hormone Replacement Therapy; D006963:Hyperphagia / Q000188:drug therapy*; D007031:Hypothalamus / Q000502:physiology; D007267:Injections; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism / Q000502:physiology*; D019257:Quinpirole / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000819:agonists*; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D013997:Time Factors
D001067:Appetite Depressants; D018491:Dopamine Agonists; D007328:Insulin; D009478:Neuropeptide Y; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D019257:Quinpirole; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine