Effects of serotonin 5-HT1/2 receptor agonists in a limited-access operant food intake paradigm in the rat

An analog of the trans-3,4-dimethyl-4-(3-hydroxyphenyl)piperidine series (LY255582) exhibits high in vitro binding affinity and antagonist potency for the μ-, δ-, and κ-opioid receptors. In vivo, LY255582 exhibits potent effects in reducing food intake and body weight in several rodent models of obesity. In the present study, we evaluated the effects of LY255582 to prevent the consumption of a highly palatable (HP) diet (a high-fat/high-carbohydrate diet) both when the food was novel and following daily limited access to the HP diet. Additionally, we examined the effects of consumption of the HP diet and of LY255582 treatment on mesolimbic dopamine (DA) signaling by in vivo microdialysis. Consumption of the HP diet increased extracellular DA levels within the nucleus accumbens (NAc) shell. Increased DA in the NAc shell was not related to the quantity of the HP diet consumed, and the DA response did not habituate following daily scheduled access to the HP diet. Interestingly, treatment with LY255582 inhibited consumption of the HP diet and the HP diet-associated increase in NAc shell DA levels. Moreover, the increased HP diet consumption observed following daily limited access to the HP diet was completely prevented by LY255582 treatment. LY255582 may be a useful tool in understanding the neural mechanisms involved in the reinforcement mechanisms regulating food intake.

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Brain GLP‐1 and the regulation of food intake: GLP‐1 action in the brain and its implications for GLP‐1 receptor agonists in obesity treatment

British Journal of Pharmacology ◽

10.1111/bph.15638 ◽

2021 ◽

Author(s):

Stefan Trapp ◽

Daniel I. Brierley

Keyword(s):

Food Intake ◽

Obesity Treatment ◽

Receptor Agonists ◽

The Brain

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Naltrexone, dopamine receptor agonists and antagonists, and food intake in rats: 1. Food deprivation

Pharmacology Biochemistry and Behavior ◽

10.1016/0091-3057(94)90476-6 ◽

1994 ◽

Vol 49 (1) ◽

pp. 197-204 ◽

Cited By ~ 15

Author(s):

David J. Hobbs ◽

James E. Koch ◽

Richard J. Bodnar

Keyword(s):

Food Intake ◽

Dopamine Receptor ◽

Food Deprivation ◽

Dopamine Receptor Agonists ◽

Receptor Agonists ◽

Receptor Agonists And Antagonists

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Central nervous system neuropeptide Y signaling via the Y1 receptor partially dissociates feeding behavior from lipoprotein metabolism in lean rats

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00351.2012 ◽

2012 ◽

Vol 303 (12) ◽

pp. E1479-E1488 ◽

Cited By ~ 11

Author(s):

Jennifer M. Rojas ◽

John M. Stafford ◽

Sanaz Saadat ◽

Richard L. Printz ◽

Annette G. Beck-Sickinger ◽

...

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Food Intake ◽

Neuropeptide Y ◽

Feeding Behavior ◽

Receptor Agonist ◽

Receptor Agonists ◽

Y1 Receptor ◽

Y2 Receptor ◽

Long Evans

Elevated plasma triglyceride (TG) levels contribute to an atherogenic dyslipidemia that is associated with obesity, diabetes, and metabolic syndrome. Numerous models of obesity are characterized by increased central nervous system (CNS) neuropeptide Y (NPY) tone that contributes to excess food intake and obesity. Previously, we demonstrated that intracerebroventricular (icv) administration of NPY in lean fasted rats also elevates hepatic production of very low-density lipoprotein (VLDL)-TG. Thus, we hypothesize that elevated CNS NPY action contributes to not only the pathogenesis of obesity but also dyslipidemia. Here, we sought to determine whether the effects of NPY on feeding and/or obesity are dissociable from effects on hepatic VLDL-TG secretion. Pair-fed, icv NPY-treated, chow-fed Long-Evans rats develop hypertriglyceridemia in the absence of increased food intake and body fat accumulation compared with vehicle-treated controls. We then modulated CNS NPY signaling by icv injection of selective NPY receptor agonists and found that Y1, Y2, Y4, and Y5 receptor agonists all induced hyperphagia in lean, ad libitum chow-fed Long-Evans rats, with the Y2 receptor agonist having the most pronounced effect. Next, we found that at equipotent doses for food intake NPY Y1 receptor agonist had the most robust effect on VLDL-TG secretion, a Y2 receptor agonist had a modest effect, and no effect was observed for Y4 and Y5 receptor agonists. These findings, using selective agonists, suggest the possibility that the effect of CNS NPY signaling on hepatic VLDL-TG secretion may be relatively dissociable from effects on feeding behavior via the Y1 receptor.

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