Both obesity and methamphetamine abuse are public health concerns. Because both behaviors may share common mechanisms, the purpose of this continuation proposal is to study the behavioral and neurochemical relationships between normal food consumption, consumption of palatable food that may lead to obesity, and smoked methamphetamine self-administration. The primary theoretical assumption is that eating high-carbohydrate palatable food or smoking methamphetamine alters the response to pharmacological manipulations known to affect feeding behavior, and these alterations can be related to brain dopamine (DA). We will determine the behavioral effects of amphetamine, dexfenfluramine, naloxone, and heroin before and during eating of palatable food, and before and during methamphetamine smoking. The secondary theoretical assumption is that intake of palatable food will be predictive of the vulnerability to smoke methamphetamine. We hypothesize that 1) eating palatable food and smoking methamphetamine will produce similar effects in manipulations presumably mediated by dopamine (amphetamine), and opioids (heroin, naloxone) without altering response to the serotonergic drug dexfenfluramine; 2) males will be more sensitive to the effects of opioids than females; 3) females will eat more palatable food and smoke more methamphetamine during the follicular phase than the luteal phase of the menstrual cycle; 4) females will be more sensitive to the effects of amphetamine during the follicular phase than males; and 5) the effects of dexfenfluramine will be independent of sex and cycle phase. Finally, we will broaden the scope of this continuation in order to explore possible receptor mechanisms underlying the responses to the various manipulations during palatable food consumption and smoked methamphetamine self-administration. We will determine 1) DA D2 receptor availability, using [11C]raclopride and Positron Emission Tomography (PET); and 2) striatal DA transmission using PET, [11C]raclopride and an amphetamine challenge before and during eating palatable food, and before and during methamphetamine smoking. We hypothesize that the direction of changes in the D2 measures will be similar, though the magnitude will vary, between palatable food and methamphetamine. We propose a series procedures in experimentally naive nonhuman primates that will allow us to prospectively examine the hypothesized relationships between intake of highly reinforcing palatable foods, stimulant abuse and underlying receptor mediated events. These studies will provide insight into both food abuse and drug abuse, and possible mechanisms mediating these two major health problems. ? ? ?
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