Co-administration of dopamine D1 and D2 Agonists additively decreases daily food intake, body weight and hypothalamic neuropeptide y level in rats

This study investigated whether co-administration of dopamine D-1 and D-2 agonists might additively inhibit the feeding effect and whether this effect was mediated by the action on hypothalamic neuropeptide Y (NPY). The D, agonist SKF 38393 (SKF) and D-2 agonists apomorphine (APO) or quinpirole (QNP) were administered, alone or in combination, to examine this possibility. In single administration, decreases of daily food intake were observed only in rats treated twice a day with a higher dose of SKF, APO or QNP. However, combined administration of D, and D-2 agonists, with each agent at a dose that alone did not induce anorexia in one daily treatment, exerted a significant effect. These results reveal that co-activation of D-1 and D-2 receptors can additively reduce daily food intake and body weight. The same treatment also decreased the level of hypothalamic NPY 24 h post-treatment. These results suggest an additive effect during combined activation of D-1 and D-2 receptor subtypes to decrease food intake and body weight that are mediated by the action of hypothalamic NPY. Similar to the effects seen in healthy rats, combined D-1/D-2 administration was also effective in the reduction of food intake in diabetic rats, revealing the efficiency of D-1/D-2 agonist in the improvement of hyperphasia in diabetic animals. Copyright (C) 2002 National Science Council, ROC and S. Karger AG, Basel.