Protocol Title: Preclinical testing of FKBP5 Inhibitors for alcohol use disorder-PTSD comorbidity
Objective:
The central hypothesis that PTSD/AUD comorbid-like phenotypes can be reversed using a highly specific FKBP5 inhibitor (SAFit2) or more broad-acting, but FDA-approved FKBP5 inhibitor (benztropine).
Hypothesis:
Aim 1: Determine whether acute administration of FKBP5 inhibitors can restore normal behavior in rats exhibiting a PTSD/AUD-like phenotype.
Aim 2: Determine whether chronic administration of benztropine inhibitors can restore normal behavior in rats exhibiting a PTSD/AUD-like phenotype.
Number of Animals to be used: n = 292 Rattus norvegicus
Study Synopsis:
This study will examine a highly specific FKBP5 inhibitor (SAFit2) and a more broad-acting, but FDA-approved FKBP5 inhibitor (benztropine)that may potentially enhance the therapeutic effect for that PTSD/AUD comorbid-like phenotypes. This research will work to determine whether acute administration of FKBP5 inhibitors can restore normal behavior in rats exhibiting a PTSD/AUD-like Phenotype and whether Chronic administration of benztropine inhibitors can restore normal behavior in rats exhibiting a PTSD/AUD-like phenotype.
The study visits are on weeks 1, 2, 4, 6, 8, 10, and 12. Primary and secondary efficacy endpoints are at week 8. At week 8, participants remain on the assigned drug or placebo for an additional 4 weeks to allow for a 12-week endpoint. Study medication is discontinued at week 12 and participants return at week 14 for evaluation of withdrawal side effects.