The extensive use of addictive drugs represents one of the major social and medical problems of our times. Information on the abuse potential of these drugs comes from studies by behavioral pharmacologists, demonstrating that animals will self-administer drugs having abuse liability in humans. Nutritional status is an environmental variable which modulates drug-seeking behavior. For example, sucrose availability has a profound effect on drug taking behavior. Rats consume significantly less morphine when given sucrose than when the sugar is removed. In the present proposal, this finding will be examined in more detail. One question which will be addressed is if the decrease in morphine consumption observed when sucrose is available is related to the palatability and/or the nutritive value of the sugar. This question will be addressed using both oral and intravenous self-administration of morphine. It is important to determine if the effects of sucrose on drug seeking behavior are limited to morphine or extend to other drugs of abuse. To extend the generality of the interaction between sucrose and drug administration, a variety of drugs including etonitazene, amphetamine, phencyclidine and methohexital will be used. Experiments which have examined the effects of oral morphine self-administration on dietary self-selection suggest that an animal's nutritional history or dietary preferences may be determinants of drug intake. To investigate this suggestion, the effects of high-fat and high-carbohydrate diets on oral morphine self-administration will be determined. Additional studies will examine the effects of nutritional history on precipitated abstinence and withdrawal from morphine. While a specific association between nutritional variables and drugs of abuse may exist, this relation also may represent a more general interaction between reinforcing substances. In the present proposal the general nature of this interaction will be investigated in studies examining the influence of other reinforcers, such as exercise, on drug self-administration. A relationship between diet and drug self-administration may have important implications for 1) the basic understanding of drug-seeking behavior and 2) the clinical treatment of drug abuse.
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