1999 — 2000 |
Bishop, Christopher R [⬀] |
F31Activity Code Description: To provide predoctoral individuals with supervised research training in specified health and health-related areas leading toward the research degree (e.g., Ph.D.). |
Effects of Nicotine On Npy Feeding and Metabolism
While there is extensive information on the deleterious effects of smoking on health, approximately 26 percent of Americans continue to smoke. One of the factors mediating onset, continuance and relapse, particularly in women, is its weight-moderating effects. Though it has been demonstrated in animal models, that nicotine, the active ingredient in smoking, produces weight loss and subsequent weight gain following cessation of nicotine administration, mechanisms responsible for this effect have yet to be elucidated. This application proposes experiments designed to identify the role of a potent orexigenic compound, neuropeptide Y (NPY), in these effects. NPY is known to significantly potentiate food intake and biochemical utilization of carbohydrates in animals when injected into the paraventricular nucleus (PVN) of the hypothalamus, and has been recently shown to be altered during nicotine administration. In the proposed experiments, nicotine, administered via Alzet pumps, would be infused for 14 days followed by an abrupt cessation (pump explantation). The proposed set of experiments will identify the differential feeding, metabolic and gender effects of NPY on nicotine over acute, chronic and post-nicotine phases. These techniques will help to characterize the role of NPY in the weight-moderating effects of nicotine as well as how it affects food intake and metabolism.
|
0.948 |
2008 — 2012 |
Bishop, Christopher R [⬀] |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Regulation of L-Dopa-Induced Dyskinesia by 5-Ht1a Receptor Mechanisms @ State University of Ny,Binghamton
DESCRIPTION (provided by applicant): Replacement therapy with the dopamine (DA) precursor L-DOPA is a highly effective treatment for the motor symptoms of Parkinson's disease (PD). Unfortunately, chronic L- DOPA administration induces abnormal involuntary movements termed L-DOPA- induced dyskinesia (LID), which severely impacts the quality of life for the individual. Given that L-DOPA will continue to be the primary treatment for PD, the long-term objective of the present application is to elucidate novel mechanisms that will improve pharmacotherapy for the reduction of LID. While the pathogenesis of LID is not well understood, excessive L-DOPA-induced corticostriatal glutamate release and post- synaptic striatal DA D1 receptors (D1R) appear essential. Unfortunately, effective anti- dyskinetic glutamate and DA receptor pharmacotherapies have proven elusive and/or far from clinical use. Recent evidence indicates that 5-HT1A receptors (5-HT1AR) constitute a viable pharmacological target for the control of LID. Despite these initial findings, the mechanism(s) by which 5-HT1AR exert their effects is largely unknown. Preliminary results from our laboratory have identified a novel striatal 5-HT1AR mechanism that appears integral to the anti-dykinetic effects of 5-HT1AR agonists. Therefore, the central hypothesis of the proposed research is that 5-HT1AR stimulation reduces LID by squelching corticostriatal glutamate release and D1R signaling in the DA-depleted striatum. This assertion will be tested using well-characterized behavioral, neurochemical and cellular techniques. The objective of this application will be accomplished by addressing 3 specific aims testing the following hypotheses: 1. Striatal 5-HT1AR stimulation attenuates LID. 2. 5-HT1AR stimulation ameliorates LID by lowering excessive corticostriatal glutamate release. 3. 5-HT1AR stimulation reduces LID by lessening overactive D1R signaling mechanisms that promote LID. Completion of these studies will enhance the field's understanding of 5-HT1A receptor regulation of movement and in so doing, advocate the use and improvement of 5-HT1AR agonists for LID treatment. PUBLIC HEALTH RELEVANCE: The movement disorder Parkinson's disease (PD) is effectively treated with the drug L-DOPA. Unfortunately chronic administration of L-DOPA leads to debilitating side effects known as dyskinesia. Studies of this application will investigate a novel pharmacologic target that shows promise in reducing dyskinesia, prolonging L-DOPA's benefit and improving the quality of life for the PD patient.
|
1 |