ACTIONS OF OPIATE DRUGS--DIETARY MODULATION

DESCRIPTION: (Applicant's Abstract) The endogenous opioid system is important for energy balance, that is, food intake and exercise. Opioid agonists increase food intake while antagonists decrease food intake. However, opioids do not uniformly affect intake of all types of foods. Rather intake of palatable foods and fluids is altered to a greater degree than intake of less palatable items. A reciprocal relationship may exist between opioids and intake of palatable fare. Intake of preferred foods moderates the behavioral consequences of opioid drugs. Similarly, exercise can mediate the effects of opioid drugs. It is hypothesized that both palatable comestibles and exercise act directly on the endogenous opioid system to influence the actions of opioids. The primary goal of this proposal is to elucidate the role of diet and exercise in moderating the behavioral outcomes of opioid agents. First, the effects of intake of palatable fluids on opioid-induced analgesia will be examined. Experiments will investigate the role of palatable ingesta in modulating the antinociceptive actions of peripherally and centrally administered opioid agonists using several tests of nociception. Second, similar experiments will be conducted to illustrate the interaction between exercise and opioid-induced analgesia. The conditioned place preference (CPP) paradigm has been used to measure the rewarding effects of drugs. The CPP paradigm will be used to determine whether intake of palatable fluids or exercise changes the rewarding effects of morphine and other opioid agents. Additionally, other studies will examine whether these factors can moderate the development of a conditioned place aversion to opioid antagonists. Intake of palatable foods may increase opioid receptor binding. If this is the case, animals with a history of consuming these foods should be more sensitive to the orexigenic actions of opioid agonists, and the anorectic effects of opioid antagonists. To test this theory, the actions of centrally and peripherally administered opioid agonists and antagonists on appetitive behaviors will be examined in animals with prior experience consuming palatable fluids. The relationship between diet and exercise and opioid drugs has implications for both the basic understanding of the endogenous opioid system, and a number of clinically relevant problems including pain management, eating disorders, and drug addiction.