Grant: Discovery Grants Program - Individual

Consistent with anecdotal reports of increased drug self-administration due to dietary constraints in humans and many similar reports from animal studies, I have found, using an animal model of relapse to drugs in rats, that acute food-deprivation stress reliably reinstates heroin and cocaine seeking. I have clearly demonstrated that there is some overlap between the brain mechanisms that underlie food deprivation- and stress (e.g., footshock)-induced reinstatement. However, this overlap is not complete and other results from my laboratory indicate that food deprivation-induced relapse to drug seeking also involves a second mechanism that taps into the energy-balance and food seeking control systems. These data point to an additional pathway through which drug seeking behavior may be modulated. These data also provide the impetus for our general hypothesis that brain systems that are associated with control of energy balance and metabolism are critically involved in the effects of drugs on behavior. My long-term goal is to determine the neural substrates that are common to significant motivators such as sex, offspring, food, and drugs of abuse. The focus of the current proposal is on two powerful incentives, drugs of abuse and food. My aim is to determine how abnormalities in the neural circuitries that are involved in appetitive behaviors can lead to the development of drug abuse and eating disorders, both of which involve a loss of control, or abnormal control, of behavior. To that end, I plan to study the motivational effects of drugs of abuse and highly palatable food to elucidate the points of the interaction between the neural circuitries involved in these appetitive behaviors. I expect this program to enhance our knowledge of the neuronal systems that are involved in the way motivated behaviors are guided by rewards and environmental challenges. Consequently, it will contribute to the understanding of the mechanisms underlying both normal and pathological human behavior.