The goal of this continuation is to study the motivational processes involved in eating behavior, and to determine how drugs that affect food consumption alter these processes. Animals will control their own pattern of daily food consumption using a procedure that provides measures of food seeking, food taking, and the motivational or incentive salience of stimuli paired with food. We hypothesize that anorectic drugs may decrease total daily food consumption by decreasing food seeking and/or food taking, which may occur independently of changes in incentive salience. We will first determine the effects of naturalistic manipulations on food-related behavior and test the generalizability of our model by studying behavior related to another reinforcer, candy. Data implicate dopamine (DA) in mediating motivational processes, with increased DA levels associated with increased incentive salience of a stimulus. Less well developed are findings that suggest that serotonin (5- HT) may also play a role in motivational processes that is oppositional to that played by DA. We will determine the effects of drugs that decrease food consumption (amphetamine, dexfenfluramine, sibutramine, acamprosate) and increase food consumption (alprazolam, delta9-THC, baclofen, MK-801), via different neurotransmitter systems, on food-related behavior. Finally, because MK-801 has been shown to slow the development of sensitization to stimulants and alter the effects of repeated administration of drugs of abuse, we will also determine whether MK-801 will alter the behavioral effects of repeated doses of amphetamine and sibutramine. This research will provide further information about the behavioral mechanisms of action of anorectic drugs with an emphasis on motivational processes. We hypothesize that drugs of abuse will alter both food seeking and the incentive salience of stimuli paired with food. A better understanding of the neuropharmacological systems that are involved in motivation will be an asset in the development of drugs that affect eating behavior and other appetitive behaviors, including drug abuse.
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