Abstract Postpartum depression (PPD) is a major health problem as it is undertreated and its pathophysiology is poorly understood. Although stress during pregnancy is a risk factor for PPD, currently there is no valid animal model of stress-induced PPO available to investigate its underlying mechanism. This thesis aimed to evaluate gestational chronic mild stress (CMS) as a valid animal model of PPD. Evaluation was done by addressing the construct, face and predictive validity. Specifically, the effect of gestational CMS in recapitulating hormone fluctuations, altering neurochemistry and behaviour, followed by reversal of CMS-induced behavioural changes by administration of chronic antidepressant drugs were assessed. Mice were either subjected to CMS or left undisturbed after the mating process until parturition. CMS involved sequential application of mild stressors (e.g. paired housing and 30° cage tilt). Exposure to gestational CMS increased the plasma corticosterone level at gestational day 13 and the level was found similarly high during late pregnancy. High-~ performance liquid chromatography analysis showed that gestational CMS altered the serotonergic levels in the hippocampus during late pregnancy. Investigation of postpartum behaviour showed no effect of CMS on maternal behaviour. However, CMS significantly increased the locomotor activity of the dams in the elevated plus maze one week after parturition and in the open field test after weaning of litters, and abolished anxiety-like behaviour in open field test. CMS impaired the retention of fear memory in contextual fear conditioning task. These results demonstrate that exposing pregnant mice to CMS resulted in changes reminiscent of PPD. Reversal of stress-induced behavioural changes could not be observed in a separate experiment, which some of the stressed mice were treated with oral clomipramine or fluoxetine at postpartum. Thus the predictive validity criterion of CMS remains to be established. In conclusion, CMS has the potential to be a valid animal model of PPD.
| Identifer | oai:union.ndltd.org:bl.uk/oai:ethos.bl.uk:594218 |
| Date | January 2013 |
| Creators | Abdul Aziz, Nur Hidayah Kaz |
| Publisher | University of Nottingham |
| Source Sets | Ethos UK |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
Page generated in 0.0068 seconds