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

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

Heather G Ward and Kenny J Simansky
Psychopharmacology, v 187(4), pp 435-446
Sep 2006
PMID: 16847679

Abstract

Naltrexone - analogs & derivatives Enkephalin, Ala-MePhe-Gly- - pharmacology Food Preferences - drug effects Receptors, Opioid, mu - metabolism Analgesics, Non-Narcotic - pharmacology Analgesics, Opioid - pharmacology Pons - drug effects Rats Male Circadian Rhythm Receptors, Opioid, mu - antagonists & inhibitors Rats, Sprague-Dawley 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer - pharmacology Feeding Behavior - drug effects Eating - drug effects Naltrexone - pharmacology Animals Time Factors Narcotic Antagonists - pharmacology Receptors, G-Protein-Coupled - antagonists & inhibitors Behavior, Animal - drug effects Pons - metabolism GTP-Binding Proteins - metabolism
Acute pharmacological studies implicate mu-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. 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. We microinfused the irreversible MOR antagonist, beta-funaltrexamine (beta-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: -Ala(2), N-Me-Phe(4), Glycinol(5)]-Enkephalin (DAMGO), 1 week after beta-FNA to probe the acute effects of exogenous stimulation of MORs on palatable food intake. [(35)S]GTPgammaS autoradiography quantified regional loss of MOR cellular function. Next, we measured the actions of beta-FNA on food intake in rats given only standard or palatable chow for 1 week. One infusion of beta-FNA persistently decreased consumption of standard but not palatable chow, regardless of feeding regimen. beta-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. beta-FNA did not affect kappa-opioid receptors. 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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Web of Science research areas
Neurosciences
Pharmacology & Pharmacy
Psychiatry
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