AS140026-A2 Haile

Protocol Title: Assessing pharmacotherapies in animal models of post-traumatic stress disorder (PTSD) and alcohol use disorder (AUD)

Objective: Evaluate the ability of FDA investigational GABAB positive allosteric modulator (PAM) medications to reduce behavioral effects of PTSD and AUD in animal models of these disorders. 


PTSD and AUD are associated with dysregulated GABAergic neurotransmission however therapeutic medications that target this system have significant adverse side effects. In contrast, GABAB PAMs have been shown clinically to exhibit a positive side effect profile.  This project will assess the GABAB PAM, ASP8062, on predator odor-induced stress and operant oral alcohol self-administration, rodent models of PTSD and AUD respectively. Results from these studies  will confirm potential mechanism of action and proof of concept enabling studies for FDA approval of human Phase II clinical trials.

Number of Animals to be used: 500 Sprague-Dawley rats (250 male, 250 female)

Study Synopsis:  PTSD and AUD often co-occur and are associated with significant adverse health consequences especially among Veterans.  Medications to treat these disorders show limited efficacy and fewhave been examined for the co-occurrence of the two disorders.  Thus, the purpose of this research program is to test promising medications in animal models of PTSD and AUD and determine if they have potential clinical therapeutic application.