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

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. [ABSTRACT FROM AUTHOR]