| Research Summary |
| Our research is concerned with the relationship between neural systems that mediate rewarding effects of food and drugs, with a particular interest in coregulation of ingestive behavior and drug-seeking by endocrine adiposity hormones (e.g. leptin, insulin) and "feeding-related" neuropeptides (e.g. AGRP, a-MSH, CART). A psychophysical curve-shift method is used in rats to measure sensitivity of brain reward circuitry to direct electrical stimulation in the presence and absence of diverse drugs of abuse. Drug reward potency is indexed by a leftward shift in the curve that relates rate of reinforcement to the brain stimulation frequency for which the animal is responding. Using this method, it has been demonstrated that persistent negative energy balance, induced by chronic food restriction, enhances sensitivity of brain reward circuitry to centrally injected psychostimulants, opiates, and NMDA antagonists. A cellular correlate of this behavioral phenomenon is the augmentation of drug-induced c-fos expression in forebrain dopamine terminal areas. This finding, together with observations of enhanced rewarding and stimulant effects of direct dopamine receptor agonists, and increased functional coupling between D-2 receptors and G-protein (i.e. quinpirole-stimulated [35S]GTPgS binding), suggests that increased dopamine receptor function is among the neuroadaptations that underlie behavioral effects of food restriction. Unlike classical sensitization processes that persist indefinitely following induction, drug reward sensitivity reverts to normal within one week of restored ad libitum feeding and weight gain. This time-course is compatible with involvement of endocrine adiposity hormones and/or "feeding-related" neuropeptides, whose levels vary dynamically with depletion and repletion of adipose stores. Current research is therefore focused in two areas: 1. Measurement of brain regional dopamine receptor-mediated signal transduction and 2. Effects of subchronic "replacement" of central insulin, leptin and anorexigenic neuropeptides in food-restricted subjects. |
| Research Information |
Research Interests | Neurobiology of Ingestive Behavior and Drug Addiction | Research Keywords | behavioral neuroscience, brain reward mechanisms, drug abuse, food restriction |
|
