The effect of light on a rat model of depression

dc.contributor.advisorRussell, Vivienne Aen_ZA
dc.contributor.advisorDimatelis, Jacqueline Jen_ZA
dc.contributor.authorMtintsilana, Asandaen_ZA
dc.date.accessioned2015-07-01T08:48:20Z
dc.date.available2015-07-01T08:48:20Z
dc.date.issued2014en_ZA
dc.descriptionIncludes bibliographical references.en_ZA
dc.description.abstractBackground: Depression is a debilitating mood disorder, negatively affecting an individual’s health and well-being. Despite this, the aetiology of depression remains poorly understood. Consistently, depression treatments are far from satisfactory due to limited efficacy and adverse side effects often associated with them, suggesting a need to improve the current animal models of depression in order to understand the basic mechanisms of the disorder. In an attempt to elucidate the pathophysiology of depression, a rodent model of depression (maternal separation, MS) is used to study the neurobiological mechanisms implicated in depression. However, MS alone produces inconsistent findings and often additional stressors are used to exaggerate the effects of MS. To create a more robust model of MS, MS rats were exposed to chronic constant light (CCL). However, contradictory findings have been reported with CCL. Aims: This study aimed to explore the effects of additional CCL in an MS model by measuring glutamate and potassium-stimulated [3H]DA release in the nucleus accumbens (NAc), testing the effects of CCL on serotonin (5-HT) levels in the hypothalamus and prefrontal cortex (PFC) and measuring ì-opioid receptor (MOR-1) levels in the NAc and orexin receptor (OXR-1 and OXR-2) levels in the PFC. Methods: In order to achieve these aims four experimental groups were chosen, out of which two groups; non-maternally separated (NMS) rats and maternally separated (MS) rats were exposed to CCL for 3 weeks during adolescence and the remaining two groups; NMS and MS rats were not subjected to CCL. At postnatal day 80 (adulthood), rats were decapitated and brain tissue collected for analysis of glutamate- and potassium-stimulated [3H]DA release in the NAc using in vitro superfusion. Serotonin levels in the hypothalamus and PFC were determined using Enzyme-Linked ImmunoSorbent Assay (ELISA). Western blot analysis was used to measure MOR-1 levels in the NAc, OXR-1 and OXR-2 in the PFC. Results: MS caused a significant decrease in glutamate-stimulated [3H]DA release in the NAc. In the NAc shell, CCL exposure revealed a trend towards a decrease in [3H]DA release in response to both glutamate- and potassiumstimulation. Moreover, in the hypothalamus NMS and MS rats subjected to CCL had significantly increased 5-HT levels compared to NMS and MS rats without xvii CCL exposure. In the PFC CCL had a significant effect on 5-HT levels and it was revealed that NMS CCL rats had decreased 5-HT levels compared to NMS rats. Similarly, MS CCL rats had significantly decreased 5-HT levels compared to NMS. MS and CCL did not have any significant effect on MOR-1 protein levels in the NAc. On the other hand, MS rats had increased OXR-1 and OXR-2 proteins levels in the PFC compared to NMS and MS CCL rats. Conclusion: MS decreased glutamate-stimulated [3H]DA release in the NAc. Serotonin levels in the hypothalamus and PFC were altered by the effects of MS and CCL. Furthermore, MS exposure increased OXR-1 and OXR-2 protein levels in the PFC. However, MS and CCL did not alter MOR-1 protein levels in the NAc. Therefore, this study has demonstrated that CCL exaggerated the effects of MS and created a more robust model of MS.en_ZA
dc.identifier.apacitationMtintsilana, A. (2014). <i>The effect of light on a rat model of depression</i>. (Thesis). University of Cape Town ,Faculty of Health Sciences ,Division of Neurosurgery. Retrieved from http://hdl.handle.net/11427/13205en_ZA
dc.identifier.chicagocitationMtintsilana, Asanda. <i>"The effect of light on a rat model of depression."</i> Thesis., University of Cape Town ,Faculty of Health Sciences ,Division of Neurosurgery, 2014. http://hdl.handle.net/11427/13205en_ZA
dc.identifier.citationMtintsilana, A. 2014. The effect of light on a rat model of depression. University of Cape Town.en_ZA
dc.identifier.ris TY - Thesis / Dissertation AU - Mtintsilana, Asanda AB - Background: Depression is a debilitating mood disorder, negatively affecting an individual’s health and well-being. Despite this, the aetiology of depression remains poorly understood. Consistently, depression treatments are far from satisfactory due to limited efficacy and adverse side effects often associated with them, suggesting a need to improve the current animal models of depression in order to understand the basic mechanisms of the disorder. In an attempt to elucidate the pathophysiology of depression, a rodent model of depression (maternal separation, MS) is used to study the neurobiological mechanisms implicated in depression. However, MS alone produces inconsistent findings and often additional stressors are used to exaggerate the effects of MS. To create a more robust model of MS, MS rats were exposed to chronic constant light (CCL). However, contradictory findings have been reported with CCL. Aims: This study aimed to explore the effects of additional CCL in an MS model by measuring glutamate and potassium-stimulated [3H]DA release in the nucleus accumbens (NAc), testing the effects of CCL on serotonin (5-HT) levels in the hypothalamus and prefrontal cortex (PFC) and measuring ì-opioid receptor (MOR-1) levels in the NAc and orexin receptor (OXR-1 and OXR-2) levels in the PFC. Methods: In order to achieve these aims four experimental groups were chosen, out of which two groups; non-maternally separated (NMS) rats and maternally separated (MS) rats were exposed to CCL for 3 weeks during adolescence and the remaining two groups; NMS and MS rats were not subjected to CCL. At postnatal day 80 (adulthood), rats were decapitated and brain tissue collected for analysis of glutamate- and potassium-stimulated [3H]DA release in the NAc using in vitro superfusion. Serotonin levels in the hypothalamus and PFC were determined using Enzyme-Linked ImmunoSorbent Assay (ELISA). Western blot analysis was used to measure MOR-1 levels in the NAc, OXR-1 and OXR-2 in the PFC. Results: MS caused a significant decrease in glutamate-stimulated [3H]DA release in the NAc. In the NAc shell, CCL exposure revealed a trend towards a decrease in [3H]DA release in response to both glutamate- and potassiumstimulation. Moreover, in the hypothalamus NMS and MS rats subjected to CCL had significantly increased 5-HT levels compared to NMS and MS rats without xvii CCL exposure. In the PFC CCL had a significant effect on 5-HT levels and it was revealed that NMS CCL rats had decreased 5-HT levels compared to NMS rats. Similarly, MS CCL rats had significantly decreased 5-HT levels compared to NMS. MS and CCL did not have any significant effect on MOR-1 protein levels in the NAc. On the other hand, MS rats had increased OXR-1 and OXR-2 proteins levels in the PFC compared to NMS and MS CCL rats. Conclusion: MS decreased glutamate-stimulated [3H]DA release in the NAc. Serotonin levels in the hypothalamus and PFC were altered by the effects of MS and CCL. Furthermore, MS exposure increased OXR-1 and OXR-2 protein levels in the PFC. However, MS and CCL did not alter MOR-1 protein levels in the NAc. Therefore, this study has demonstrated that CCL exaggerated the effects of MS and created a more robust model of MS. DA - 2014 DB - OpenUCT DP - University of Cape Town LK - https://open.uct.ac.za PB - University of Cape Town PY - 2014 T1 - The effect of light on a rat model of depression TI - The effect of light on a rat model of depression UR - http://hdl.handle.net/11427/13205 ER - en_ZA
dc.identifier.urihttp://hdl.handle.net/11427/13205
dc.identifier.vancouvercitationMtintsilana A. The effect of light on a rat model of depression. [Thesis]. University of Cape Town ,Faculty of Health Sciences ,Division of Neurosurgery, 2014 [cited yyyy month dd]. Available from: http://hdl.handle.net/11427/13205en_ZA
dc.language.isoengen_ZA
dc.publisher.departmentDivision of Neurosurgeryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.subject.otherNeurosciencesen_ZA
dc.titleThe effect of light on a rat model of depressionen_ZA
dc.typeMaster Thesis
dc.type.qualificationlevelMasters
dc.type.qualificationnameMSc (Med)en_ZA
uct.type.filetypeText
uct.type.filetypeImage
uct.type.publicationResearchen_ZA
uct.type.resourceThesisen_ZA
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