Food deprivation increases the mRNA expression of μ-opioid receptors in the ventral medial hypothalamus and arcuate nucleus

Activation of mu-opioid receptors makes animals hyperphagic and increases their preference for a high-fat diet. Previous studies have suggested that this receptor population plays a role in mediating the hyperphagia that is associated with food deprivation. In this paper, we tested the hypothesis that food deprivation will increase the expression of mu-opioid receptors in the ventral medial hypothalamus and arcuate nucleus (VMH/ARC). Food deprivation resulted in a significant increase in the mRNA expression of mu-opioid receptors in the VMH/ARC and the lateral hypothalamus (LH) after 48 h of fasting but not after 24 or 12 h of fasting in either the light or dark. We did not observe a change in the mRNA expression of kappa- or delta-opioid receptors after food deprivation. When food-deprived animals were given a choice between a low-fat diet and a high-fat diet, they were hyperphagic and consumed significantly more of the high-fat diet. When the mu-opioid receptors were blocked with beta-funaltrexamine (selective mu-opioid receptor antagonist), prior to giving food-deprived animals access to both a low-fat and high-fat diet, it significantly decreased the percentage of high-fat diet consumed. These data demonstrate that hypothalamic mu-opioid receptors may contribute to the hyperphagia and increased preference for a high-fat diet that is associated with food deprivation.