The importance of endogenous opioids in feeding behavior

Abstract

Endogenous opioids are involved in a broadly distributed neural network regulating eating behavior. Opioid transmission has long been implicated in controlling hedonic and homeostatic feeding as well as regulating body weight and metabolism. Most evidence implicating endogenous opioids is based on studies using pharmacological, or genetic knockout of opioid receptors, which alters feeding behaviors. However, individual contribution of each opioid peptide in feeding behavior and metabolism is not entirely clear.<br /> The present study was aimed to distinguish the role of the two major classes of endogenous opioids, namely enkephalin and dynorphin, in the motivational aspect of feeding behavior. Prodynorphin knockout and proenkephalin knockout mouse models were presented with highly palatable chocolate-flavored pellets and tested in an operant-self administration paradigm. The results suggest that the endogenous peptides dynorphin and enkephalin are involved in the modulation of hedonic control of feeding behavior. The second aim of the study was to elucidate the impact of dynorphin in modulation in the body weight and metabolism after prolonged voluntary palatable high-fat food consumption. Prodynorphin deficient and wild-type mice were maintained for 12 weeks on a high-fat diet (60% fat) or a normal chow with either a time-restricted access (8 hours) to food or an <em>ad libitum</em> access to food. The outcomes from the present study demonstrate the crucial role of endogenous opioid dynorphin in the regulation and maintenance of body weight. Blood glucose levels were modulated in high-fat diet-fed female mice, whereas, food consumption in animals was unaltered. Furthermore, prodynorphin deficient animals displayed significantly reduced levels of hypothalamic orexigenic peptides NPY and orexin-A under different feeding regimens.<br /> The present study gives a first insight about the modulation of metabolic and endocrine changes associated with diet composition and feeding regimen by endogenous opioid dynorphin. The study also demonstrates the involvement of the opioid peptides dynorphin and enkephalin in hedonic control of feeding behavior.