Efficacy and mechanism of action of intrahippocampal D-cycloserine in an animal model of post-traumatic stress disorder

Abstract

Listen

Translate article

Event Abstract Back to Event Efficacy and mechanism of action of intrahippocampal D-cycloserine in an animal model of post-traumatic stress disorder Lorren Fairbairn1*, Soraya Seedat1 and Willie Daniels2 1 University of Sellenbosch, Department of Psychiatry, South Africa 2 University of Kwazulu-Natal, South Africa Background: One of the most prevalent anxiety disorders is posttraumatic stress disorder (PTSD), of which current therapies are based on the processes of fear extinction. Specifically cognitive behaviour therapy (exposure-based) in humans is procedurally very analogous to extinction training in animal models of emotional learning [1].Recent studies have alluded to the mechanisms underlying fear extinction which in turn has given rise to the hypothesis that dysfunctional fear extinction plays a vital role in the development of PTSD pathophysiology. DCS and its facilitative effects are currently under investigation in clinical studies of PTSD in order to enhance fear extinction techniques. However, attempts to identify specific mechanisms by which DCS enhances loss of fear in humans have provided few insights. Considering the known impact of trauma and stress on early brain development, further studies need to be conducted in order to elucidate the mechanisms underlying PTSD symptomatology in adolescents. Aim: Therefore the proposed animal study aims to extend the current state of knowledge of the effects of DCS on anxiety reduction in adolescent and adult rats, hypothesizing that these are associated with adaptive learning. Methodology: Since associative fear conditioning and non-associative sensitization processes have been suggested as contributors towards exaggerated implicit fear memory [2], a PTSD model tapping into both of these fear components following the experience of a trauma, will be used. A brief but intense electric footshock will be applied [3]. Behaviour, neurotrophin levels, gene expression and protein synthesis will be measured.Results:Pending.Should be available in time for congress. Significance: The proposed study is of significant value in addressing the molecular mechanisms of PTSD in the context of the current limited availability of effective therapeutic strategies for fear extinction.