Neurological mechanisms relevant to intermittent episodes of behavioral excess are not well understood, but bear investigation due to the contribution of this kind of behavior to health problems such as disordered eating, obesity and substance abuse. We have developed a unique rat bingeing protocol, which we have been using to examine the neurobiology associated with repeated intermittent excessive fat intake that is maintained over extended periods of time. Peptides that regulate fat intake under non-binge conditions are without effect when rats binge on fat. In contrast, recent results from my laboratory show that the GABA-B agonist baclofen reduces fat intake in our protocol, while having no effect in non-bingeing protocols. Others have reported that baclofen reduces self-administration of abused drugs. This suggests that the neurobiology of bingeing is different from that of non-binge behavior, but may share similarities with the neurobiology of substance abuse. Therefore, we will use baclofen to test the overall hypothesis guiding this research, i.e. that GABA-B receptors have a role in binge-type eating. The following Specific Aims will be addressed:
AIM 1 : To test the hypothesis that GABA-B ligands will differentially affect fat consumption in bingeing and non-bingeing rats. Hypotheses: a) Lower dosages of baclofen will reduce food intake to a greater extent in bingeing rats than in non-bingeing rats; Lower dosages of baclofen will reduce food intake to a greater extent in females than in males; b) Baclofen-induced reductions in binge intake will be mediated centrally; GABA-B receptor blockade will stimulate binge intake; c) Dosages of GABA-B ligands that affect food intake will not affect general behavioral activity in the bingeing rats.
AIM 2 : To test the hypothesis that baclofen-induced reductions in fat intake are enhanced with repeated bingeing. Hypothesis: Lower dosages of baclofen will reduce food intake to a greater extent in rats that have repeatedly binged than in rats that have engaged in fewer binge episodes.
AIM 3 : To test the hypothesis that the VTA is a sensitive site of action for baclofen-induced reductions in bingeing. Hypothesis: Lower doses of baclofen will reduce bingeing when infused into the VTA than when infused into the striatum or substantia nigra. These studies are the first to examine the contribution of GABA-B receptors to bingeing and will provide new insight into the neurobiology of bingeing-related disorders
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