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dc.contributor.advisorOlszewski, Pawel K.
dc.contributor.authorBray, Jonathon Edward
dc.date.accessioned2023-04-11T23:15:11Z
dc.date.available2023-04-11T23:15:11Z
dc.date.issued2022
dc.identifier.urihttps://hdl.handle.net/10289/15677
dc.description.abstractAutism spectrum disorder (ASD) is a complex disorder whose etiology lies in, among others, abnormal neural processing, and improper neural circuitry development. This results in a plethora of aberrant behaviors, including those driven by the brain’s reward system and by the endogenous mediators of reward, for example opioids. One of the maladaptive consequences of pathophysiology of the reward system is excessive consumption of palatable foods in people with autism and in ASD model animals, such as valproic acid (VPA)-induced ASD rats. Here, I hypothesized that overconsumption of palatable diets in the VPA ASD rat is caused by abnormal functioning of the opioid circuitry. To investigate this, first I determined sensitivity of sucrose liquid-fed or high?fat high-sugar chow (HFHS)-fed VPA vs non-VPA control rats to the anorexigenic properties of the opioid receptor antagonist, naltrexone (NTX), a drug that reduces eating for palatability, but does not affect feeding for calories. In the follow up immunohistochemical study involving a marker of neuronal activity, c-Fos, I examined differences in brain activation after an injection of the same dose of NTX in VPAs vs non-VPA controls. As expected, NTX did not affect energy-driven consumption of bland chow in non-VPA controls or VPAs. NTX did, however, decrease intake of palatable sucrose water and HFHS chow. Importantly, while 1 mg/kg NTX was sufficient to reduce eating for palatability in non-VPA controls, a 10-mg NTX dose was needed to achieve the same effect in VPAs. c-Fos analysis in the non–VPA controls showed significant differences in neuronal activation in the paraventricular nucleus (PVN), supraoptic nucleus (SON), arcuate nucleus (ARC), Dorsomedial hypothalamus (DMH), central nucleus of the amygdala (CeA), and nucleus accumbens shell (NAc – shell). The VPA animals showed a difference only in the CeA. Collectively these data show different responsiveness to NTX at the behavioural (feeding) and brain activation iii (c-Fos) level, likely indicative of dysregulation of the opioid signaling and – more broadly – reward processing, in the autistic brain.
dc.format.mimetypeapplication/pdf
dc.language.isoen
dc.publisherThe University of Waikato
dc.rightsAll items in Research Commons are provided for private study and research purposes and are protected by copyright with all rights reserved unless otherwise indicated.
dc.subjectNaltrexone
dc.subjectVPA
dc.subjectASD
dc.subjectAutism
dc.subjectc-Fos
dc.subjectAbberant reward processing
dc.subjectOpioid system
dc.subjectEndogenous opioids
dc.subjectImmunohistochemistry
dc.subjectHigh-Fat-High-Sugar
dc.subjectFood intake
dc.subjectPalatable food intake
dc.subjectPalatability driven intake
dc.subjectSupraoptic nucleus (SON)
dc.subjectParaventricular nucleus (PVN)
dc.subjectDorsomedial hypothalamus (DMH)
dc.subjectArcuate nucleus (ARC)
dc.subjectCentral nucleus of the amygdala (CeA)
dc.subjectNucleus accumbens shell (NAc – shell)
dc.subjectnucleus accumbens core (NAc – core)
dc.subjectSucrose
dc.subject.lcshRats -- Behavior
dc.subject.lcshRats -- Physiology
dc.subject.lcshRats -- Feeding and feeds
dc.subject.lcshAppetite -- Physiological aspects
dc.subject.lcshOpioids -- Receptors -- Physiological aspects
dc.subject.lcshNeurochemistry
dc.subject.lcshAutism spectrum disorders -- Physiological aspects
dc.subject.lcshAutistic people -- Physiology
dc.subject.lcshNaltrexone -- Physiological aspects
dc.subject.lcshAppetite depressants -- Physiological aspects
dc.subject.lcshReward (Psychology) -- Physiological aspects
dc.titleInsensitivity to anorexigenic effects of naltrexone in the VPA rat model of autism
dc.typeThesis
thesis.degree.grantorThe University of Waikato
thesis.degree.levelMasters
thesis.degree.nameMaster of Science (Research) (MSc(Research))
dc.date.updated2023-01-07T09:00:38Z
pubs.place-of-publicationHamilton, New Zealanden_NZ


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