Ethopharmacological approaches to the study of fear learning and memory: focus on the mTOR Kinase pathway and predator stress models

Whiteman, Jesse (2017) Ethopharmacological approaches to the study of fear learning and memory: focus on the mTOR Kinase pathway and predator stress models. Masters thesis, Memorial University of Newfoundland.

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Abstract

Traumatic experiences (rape, assault, combat) can cause Post-Traumatic Stress Disorder (PTSD), a source of substantial psychological suffering in those so affected. PTSD is defined by symptoms of traumatic re-experiencing, avoidance, and increased startle response (hyperarousal), along with disruptions in mood and cognition. The substantial social and individual burdens of the disorder strongly motivate research into its neural basis. Predator Stress (PS) models have been introduced to the literature over the last 30 years in order to facilitate this. However, the cat exposure test (Adamec & Shallow, 1993) has proven variable in its effects on rodent subjects. The experiments described here were performed with the aim of developing a more reliable and robust predator stress-based animal model of PTSD. Experiment 1 tested whether predator vocal sounds (cat calls) produced a PTSD-like phenotype in rats, and did not produce any significant effects. Experiment 2 modified the Rat Exposure Test (RET; Yang et al., 2004) and demonstrated predator stress effects on measures of contextual fear memory, anxiety-like behaviour, and hyperarousal, suggesting the RET is a useful model of PTSD. Experiment 3 tested whether inhibition of the mTOR kinase pathway with Rapamycin (RAP) would attenuate the consolidation of these memories. RAP blocked contextual fear memories and attenuated anxiety, but the effects of the RET were not as consistent as in Experiment 2. Reasons for the continued variability in predator stress models (and the neuroscience of learning in general) are discussed.

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