Posttraumatic stress disorder (PTSD) is an anxiety disorder that may result from an exposure
to a severely traumatic life-event. It is characterised by a delayed onset of psychological and
physical symptoms including re-experiencing the event, avoidance of reminders associated with
the trauma, increased autonomic arousal and distinct memory deficits. This disorder is also
characterised by a maladaptive hypothalamic-pituitary-adrenal (HPA)-axis response and altered
monoamine concentrations in the hippocampus and pre-frontal cortex.
The Time Dependent Sensitization (TDS) model is a putative animal model of PTSD that is
based on the concept of repeated trauma, using three acute stressors (TS) of intense severity
followed by a mild situational reminder (RS) on day 7 subsequent to the acute stressors. The
aims of this study were to determine if the Triple Stressor (TS) induces stress and if the
situational reminder (RS) is necessary for the maintenance of the stress response over time and
whether these two stress responses are qualitatively and quantitively different. This was done to
further validate the TDS model and to characterize the development and progression of the
stress-related pathology of PTSD.
Methods used were High Performance Liquid Chromatography (HPLC) with electrochemical
detection (biochemical correlates) for quantifying the monoamines dopamine (DA),
noradrenaline (NA) and serotonin (5-HT) concentrations in the hippocampus and pre-frontal
cortex (PFC); radio immuno assay (RIA) for the determination of plasma corticosterone
concentrations (neuroendocrine parameter) and the use of the Elevated Plus Maze (EPM) to
detect anxiety-like behaviour (behavioural analyses).
The study was subdivided into an Acute and Re-Stress study (n = 10). In the Acute Study rats
were exposed to TS as the only stressor. Group 1 was sacrificed immediately after TS, Group 2
was sacrificed 3 days post TS and Group 3 on day 7 post TS. In the Re-Stress Study both TS
and RS were used as stressors. Group 4 was sacrificed immediately after the situational
reminder, Group 5 was sacrificed 3 days post RS and Group 6 on day 7 post RS. A group of
unstressed rats were used as Control.
The results of this study found corticosterone concentrations elevated immediately after the TS
(p<0.05). Exposure to the RS resulted in a profound hypocortisolism (p<0.05). These results
indicate a possible disturbance in the regulation of the HPA-axis, which manifests as an
enhanced negative feed-back upon re-introduction of the stressful situation.
Changes in MA concentrations were evident. Although no definite fixed trend is apparent in this
study, it is evident that the TDS model does induce monoamine dysregulation. Hippocampal
NA. DA and 5-HT concentrations were noted to be elevated on day 7 post TS (p<0.05). On day
7 post RS only hippocampal 5HT was decreased significantly (p<0.05).
Behavioural analyses indicate that stress related anxiety was not sustained after the TS but 7
days after the exposure to the RS rats were most anxious (p<0.05). The results confirm that the
TDS model does induce PTSD-like symptoms in rats and that the situational reminder (RS) is
necessary for the maintenance of the stress response. This model may be useful in the
investigation of future experimental pharmacological interventions in the management of PTSD. / Thesis (M.Sc. (Pharmacology))--North-West University, Potchefstroom Campus, 2005.
| Identifer | oai:union.ndltd.org:NWUBOLOKA1/oai:dspace.nwu.ac.za:10394/587 |
| Date | January 2004 |
| Creators | Jeeva, Zakkiyya Igbal |
| Publisher | North-West University |
| Source Sets | North-West University |
| Detected Language | English |
| Type | Thesis |
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