Modulation of feeding and locomotion through mu and delta opioid receptor signaling in the nucleus accumbens

Abstract 

Opioid signaling has been strongly implicated in driving palatable food consumption. The nucleus accumbens (NAcc) is one important site of this effect; hyperphagia elicited by administration of exogenous mu opioid receptor (MOR) ligands in this brain region has been well documented. However, the role that endogenous opioid ligands in the NAcc play in controlling food intake remains poorly understood. Enkephalins, which signal through both the MOR and delta opioid receptor (DOR), are highly expressed within a subset of NAcc neurons, and have been shown to be sensitive to manipulations of diet and motivation. To investigate a potential role for these signaling molecules in regulating palatability-driven consumption, we measured high fat chow intake in rats following a series of pharmacological manipulations of NAcc opioid signaling. NAcc infusion of the MOR agonist [d-Ala2, N-MePHe4, Gly-ol]-enkephalin (DAMGO) robustly increased palatable food intake, as has previously been demonstrated. In contrast, neither infusion of Met-enkephalin, its synthetic analogue [d-Ala2] Met-enkephalin (DALA) nor the DOR-specific ligand [d-Pen2, Pen5]-enkephalin (DPDPE) had significant effects on food intake. However, when administered in combination with DAMGO, DPDPE significantly suppressed the magnitude of DAMGO-evoked feeding. Further analysis of DPDPE effects revealed that the drug strongly increased locomotor activity. Suppressive effects on feeding, then, may have occurred through competition between feeding and locomotion for behavioral expression.

Abbreviations: β-FNA, beta-funaltrexamine, DADLE, [d-Ala2, d-Leu5]-enkephalin, DALA, [d-Ala2] Met-enkephalin, DALCE, [d-AlaLeu5, Cys6]-enkephalin, DAMGO, [d-Ala2N-MePHe4, Gly-ol]-enkephalin, DOR, delta opioid receptor, DPDPE, [d-Pen2Pen5]-enkephalin, KOR, kappa opioid receptor, MOR, mu opioid receptor, NAcc, nucleus accumbens, Nor-BNI, Nor-binaltorphimine, PPENK, preproenkephalin

Keywords: Palatability, Food intake, Consumption, Enkephalin, Nucleus accumbens