Post-Stress Combined Administration of Beta-Receptor and Glucocorticoid Antagonists as a Novel Preventive Treatment in an Animal Model of PTSD
Annual rept. 1 Jul 2008-30 Jun 2009
TEXAS UNIV HEALTH SCIENCE CENTER AT SAN ANTONIO
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Some PTSD symptoms, e.g., social withdrawal, generalized anxiety and stress-sensitization, may reflect pathologically enhanced memory of traumatic stress. Stress-induced secretion of brain norepinephrine and glucocorticoids GC activate beta- receptors and GC-receptors in the amygdala, enhancing consolidation of emotional memories. Thus, giving a beta-antagonist plus a GC-antagonist immediately after stress might decrease the strength of those associations, and prevent the emergence of PTSD. The goals of this work were to 1 validate Massed Footshock MFS, in which rats are exposed to a single session of repeated footshock, as a model of PTSD 2 establish a reliable test battery of PTSD-like behaviors in rats and 3 test the combined drug treatment after MFS. We established a reliable test battery for PTSD-like behavior, and drug treatment did not interfere with testing, nor induce non-specific effects. However, MFS proved to be neither a valid nor useful model of PTSD. It failed to affect the most relevant behavioral measures, and confounded fear conditioning. Thus, for the remainder of this project, we plan instead to employ a modified Single Prolonged Stress SPS model, that has been reported to elicit relevant behavioral effects and retains the temporal features of MFS that made it amenable to acute pharmacological intervention.
- Anatomy and Physiology
- Medicine and Medical Research
- Stress Physiology