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Title: A model of depression : assessment of the validity of the chronic mild stress procedure
Author: Cheeta, S. K.
Awarding Body: University College of Swansea
Current Institution: Swansea University
Date of Award: 1995
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Chronic sequential exposure to a variety of mild stressors has been shown to cause a subsensitivity to rewards (anhedonia), which is reversible by chronic treatment with antidepressant drugs and has thus been proposed as an animal model of depression. The aim of the present research was to assess further the predictive, face and construct validity of the Chronic Mild Stress (CMS) procedure. Chapter 2 replicated earlier findings that stressed animals decrease consumption of a palatable weak (1%) sucrose solution and show impaired place preference conditioning. The predictive validity of the CMS procedure was supported by the finding that these behavioural deficits were reversed by chronic treatment with the atypical antidepressant mianserin. The (+)-enantiomer of mianserin, which is thought to be the active component of the racemic compound was also effective. Treatments that were found to be ineffective included the (-)-enantiomer of mianserin, the alpha-2 antagonist RX811059 and the 5-HT2 antagonist ritanserin. Animals treated with these drugs showed behavioural deficits that were similar to vehicle treated stressed animals. In animals successfully treated with antidepressants the deficits in sucrose intake were reinstated by acute pre-treatment with the specific dopamine D2/D3 antagonist raclopride. The face validity of the CMS procedure was assessed at a biological level. Two experiments in Chapter 3 demonstrated that chronically stressed animals displayed abnormalities in their sleeping patterns including increases in the duration of, and transitions into REM sleep and a reduced latency to the onset of the first REM period. The above findings support the validity of the CMS procedure as a model of depression. The findings suggest that antidepressants work in this model by sensitising D2/D3 receptors, thus supporting the hypothesis that the mesolimbic DA system has an important role in the mechanism of action of antidepressant drugs and in aspects of the pathophysiology of depression.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available