Includes bibliographical references. / 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.
| Identifer | oai:union.ndltd.org:netd.ac.za/oai:union.ndltd.org:uct/oai:localhost:11427/13205 |
| Date | January 2014 |
| Creators | Mtintsilana, Asanda |
| Contributors | Russell, Vivienne A, Dimatelis, Jacqueline J |
| Publisher | University of Cape Town, Faculty of Health Sciences, Division of Neurosurgery |
| Source Sets | South African National ETD Portal |
| Language | English |
| Detected Language | English |
| Type | Master Thesis, Masters, MSc (Med) |
| Format | application/pdf |
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