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Chronic prevention of μ-opioid receptor (MOR) G-protein coupling in the pontine parabrachial nucleus persistently decreases consumption of standard but not palatable food

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Abstract

Rationale

Acute pharmacological studies implicate μ-opioid receptors (MORs) in the parabrachial nucleus (PBN) of the brainstem in modulating eating. The long-term effects of preventing the cellular function of parabrachial MORs on food consumption remain to be elucidated.

Objectives

To determine whether (1) chronic inhibition of MOR-mediated G-protein coupling in the PBN of rats would persistently reduce eating and (2) food properties dictate the effects of MOR blockade.

Materials and methods

We microinfused the irreversible MOR antagonist, β-funaltrexamine (β-FNA) into the lateral PBN and measured the intake of standard and calorically dense palatable chow for 1 week. First, rats were given standard chow for 20 h daily and a calorically dense palatable chow for 4 h during the day. We infused the agonist, [d-Ala2, N-Me-Phe4, Glycinol5]-Enkephalin (DAMGO), 1 week after β-FNA to probe the acute effects of exogenous stimulation of MORs on palatable food intake. [35S]GTPγS autoradiography quantified regional loss of MOR cellular function. Next, we measured the actions of β-FNA on food intake in rats given only standard or palatable chow for 1 week.

Results

One infusion of β-FNA persistently decreased consumption of standard but not palatable chow, regardless of feeding regimen. β-FNA also blocked DAMGO-stimulated palatable chow intake, prevented DAMGO-stimulated G-protein coupling in the central and external lateral subnuclei of the PBN, and decreased coupling in the medial PBN. β-FNA did not affect κ-opioid receptors.

Conclusions

MORs in the lateral PBN serve a physiological role in stimulating consumption of standard food. Properties of the diet, such as high palatability or caloric density, may override the influence of inhibiting MOR function.

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Acknowledgements

The authors thank Dr. Vincent Aloyo for his helpful comments about the manuscript and Alicia Spor and Adam Phillips for their technical assistance. This work was supported by USPHS Grant DK067648 from the National Institute of Diabetes and Digestive and Kidney Diseases to KJS.

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  1. Department of Pharmacology and Physiology, Drexel University College of Medicine, 245 N 15th Street, MS 488, Philadelphia, PA, 19102, USA

    Heather G. Ward & Kenny J. Simansky

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  1. Heather G. Ward
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  2. Kenny J. Simansky
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Correspondence to Kenny J. Simansky.

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Ward, H.G., Simansky, K.J. Chronic prevention of μ-opioid receptor (MOR) G-protein coupling in the pontine parabrachial nucleus persistently decreases consumption of standard but not palatable food. Psychopharmacology 187, 435–446 (2006). https://doi.org/10.1007/s00213-006-0463-7

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