Co-Administration of Dopamine D₁ and D₂ Agonists Additively Decreases Daily Food Intake, Body Weight and Hypothalamic Neuropeptide Y Level in Rats

Abstract

This study investigated whether co-administration of dopamine D₁ and D₂ agonists might additively inhibit the feeding effect and whether this effect was mediated by the action on hypothalamic neuropeptide Y (NPY). The D₁ agonist SKF 38393 (SKF) and D₂ 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 D₁ and D₂ 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 D₁ and D₂ 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 D₁ and D₂ 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 D₁/D₂ administration was also effective in the reduction of food intake in diabetic rats, revealing the efficiency of D₁/D₂ agonist in the improvement of hyperphasia in diabetic animals.

Nicotine, Body Weight and Potential Implications in the Treatment of Obesity

“…Accordingly, they suggested that a deficiency in the dopaminergic receptor binding promoted overeating to compensate for this lack of dopaminergic activity. Similarly, co-administration of D1 and D2 agonists (i.e., SKF 38393 + apomorphine or quinpirole) was found to result in reduced daily food intake and body weight in rats [36]. Dopamine's effect on food intake also seems to be mediated through its actions within the hypothalamus.…”

Dopamine Transporter Gene (DAT1) Associated with Appetite Suppression to Methylphenidate in a Case–Control Study of Binge Eating Disorder

“…DA is one of the most salient neurotransmitters in the reinforcement value of food and the regulation of its intake (Epstein et al, 2002). Although drugs that substantially increase brain DA tend to induce anorexia in animals (eg Bina and Cincotta, 2000;Kuo, 2002), there is considerable variation in response magnitude across human subjects. In a recent study with a small group of obese adults, Leddy et al (2004) found that approximately equal numbers showed either a large decrease, a small/moderate Comparisons between the groups were made using one-way ANOVA for the continuous variables and w 2 tests for the categorical data.…”

Characterization and mapping of bovine dopamine receptors 1 and 5

“…2001). Furthermore, interaction of the DRDs with other factors implicated in obesity, such as neuropeptide Y (NPY), corticotropin releasing hormone (CRH), have been demonstrated (Bina & Cincotta 2000; Kuo 2002). In spite of this evidence, very little is known about the dopamine receptors in cattle with the exception of DRD2 , which has been completely sequenced (Chio et al .…”