The Effects of Mu and Kappa Opioid Antagonists on Reinstatement of Sugar Seeking

Excessive consumption of palatable food is related to death caused by cardiovascular disease, fatty liver disease, and diabetes in humans and animals. Resumption of consuming palatable food following abstinence can be thought of as relapse. Reinstatement of sugar seeking in rats serves as animal model for studying relapse to excessive consumption of palatable foods in humans. Given the known role of mu and kappa receptors in hedonic eating, satiety, stress and food seeking, and food-restriction induced drug seeking, it was predicted that Naltrexone (mu-opioid antagonist; doses: 0.3 mg/kg and 3 mg/kg) and JDTic (kappa-opioid antagonist; doses: 3 mg/kg and 10 mg/kg) drugs should prevent reinstatement of sugar seeking caused by food-restriction stress and by priming. Rats were trained to self-administer sugar in an eight arm radial apparatus where tests of seeking and consumption were also tested. It was found that NTX, but not JDTic, blocked reinstatement caused by food-restriction. While these two antagonists had opposite effects on sucrose self-administration during reacquisition, both attenuated the effects of food restriction on reinstatement induced by the sugar prime. Furthermore JDTic appeared to dose dependently enhance nose poking in food restricted rats during the test of prime-induced reinstatement. These data confirm the critical role of opioid systems in sugar consumption and sugar seeking, further demonstrate the clinical relevance of using mu-opioid antagonists to treat problematic eating and warrant further investigation of a role for kappa opioid receptors in feeding related behaviour.