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The Effect of Excess Dietary Fat on Behavioral and Reward Circuit Plasticity
Başlık:
The Effect of Excess Dietary Fat on Behavioral and Reward Circuit Plasticity
Yazar:
Dingess, Paige M., author.
ISBN:
9780438021013
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (169 pages)
Genel Not:
Source: Dissertation Abstracts International, Volume: 79-10(E), Section: B.
Advisors: Travis Brown Committee members: Francis Flynn; Sreejayan Nair; Daniel Rule; Stephen Santoro.
Özet:
More than one third of the United States population is diagnosed with obesity, a multifaceted disease with many contributing factors. It is without question though that excess dietary fat facilitates adipose tissue accumulation and expedites obesity onset. Yet, the behavioral and neurobiological mechanisms underlying the development and maintenance of maladaptive feeding are not well understood. To investigate these mechanisms, we utilized two primary methods. First, a behavioral operant paradigm known as "incubation of craving" in which rats learn to self-administer a food pellet reward (high-fat or chow), delivered in conjunction with associative cues (light + tone). Incubation of craving refers to the increased responsiveness to these cues over time and is a phenomenon hypothesized to promote relapse and maladaptive reward seeking. Secondly, to examine structural plasticity among both excitatory and inhibitory neurons, we quantified dendritic spines and perineuronal nets (PNNs), respectively, in key reward circuit regions. The goal of Chapter 1 was to elucidate differences in the incubation of high-fat (HF) and chow craving. In part I we demonstrated that rats readily prefer the HF pellets but exhibit incubation of craving for both HF and chow cues following a short-duration self-administration training protocol (2 hrs/day for 10 days). Further investigation revealed that rats prefer the novel chow pellets to the chow bricks they receive in their home cage and that rats exclusively reared on chow pellets fail to display incubation of chow craving. In part II we implemented an extended access self-administration training protocol (6 hrs/day for 10 days), in an effort to overcome the effect of novelty, and found that rats again show incubation of craving for both HF and chow cues but that the responsiveness to HF cues is significantly greater. We further demonstrated that incubation of both HF and chow craving is associated with synapse maturation in the nucleus accumbens, a region of reward integration. The objective of Chapter 2 was to examine prefrontal structural plasticity following exclusive maintenance on a 60% HF diet. We found that three weeks of HF consumption reduced dendritic spine density in the infralimbic prefrontal cortex as well as the intensity of PNN staining in the prelimbic prefrontal cortex and orbitofrontal cortex. This effect was observed in animals fed the HF diet in a restricted manner such that their weight gain and adiposity did not differ from controls, suggesting these effects are more likely due to fat exposure rather than weight gain. The goal of chapter 3 was to investigate the role of genetic and environmental factors in the above plasticity. We first demonstrated that selectively bred obesity prone but not obesity resistant rats display structural deficits to PNNs of the prefrontal cortex, as observed in the outbred strain. We also showed that obesity resistant rats consume less food after fasting and require more time to receive the same number of pellets received by the outbred strain in the self-administration protocol. Finally, we utilized a high-intensity interval training regimen to block incubation of HF craving. Taken together, these studies provide novel insights to the neural and behavioral consequences of excess fat exposure and may therefore guide therapeutic efforts in the treatment of obesity.
Notlar:
School code: 0264
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Yer Numarası | Demirbaş Numarası | Shelf Location | Lokasyon / Statüsü / İade Tarihi |
---|---|---|---|
XX(680940.1) | 680940-1001 | Proquest E-Tez Koleksiyonu | Arıyor... |
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