Glutamate Transmission Enhancement for Treatment of PTSD
Abstract
Exposure therapy, a fear extinction based treatment, has been shown to be effective in treating post traumatic stress disorder (PTSD). Exposure-based therapies require substantial time and investment for both the patient and provider, averaging 10 sessions or more of approximately 1 h each to achieve significant beneficial effects. Thus, treatments that enhance the efficacy of extinction therapies and reduce the number of required sessions for remission would be of great benefit. Ideally, such therapy strategies may reduce the need for long term medication. This proposal uses a preclinical animal model of fear learning and extinction (fear potentiated startle) to test the efficacy of two novel compounds that enhance glutamate signaling. Previous reports indicate that the partial glutamate receptor agonist D-cycloserine (DCS) has been shown to facilitate animal models of extinction which has translated into recent clinical reports of efficacy in anxiety disorders when administered during extinction based psychotherapies. DCS however, has been shown to have some limitations in both dosing and efficacy in some circumstances however (Norberg, Krystal, & Tolin, 2008). Here we will examine the efficacy of glycine transporter (GLYT1) inhibition and positive alloseric modulation of AMPA receptors in facilitation fear extinction. GLYT1 inhibitors are reported to show significantly greater enhancement of glutamate signaling compared to DCS (Sur and Kinney, 2007), as well as facilitate glutamate transmission in limbic regions that modulate emotional processes. We will examine the efficacy of treatment with a glycine transporter inhibitor during extinction training to enhance fear extinction retention and reduce fear reinstatement in mice.
Document Details
- Document Type
- Technical Report
- Publication Date
- Mar 01, 2009
- Accession Number
- ADA506358
Entities
People
- Victoria B Risbrough
Organizations
- University of California Regents