Research Projects - concluded

Concluded Extend and Confirm Projects funded by the ITN


Translational Mouse Models of PTSD and Comorbid Substance Use
Principal Investigator(s): Eric R. Kandel, M.D.
Lay Abstract Identify causal biological mechanisms of PTSD using a novel gene x environment mouse model of stress vulnerability, and characterize the interaction between PTSD-like symptoms and nicotine/alcohol consumption
Identify SNPs associated with PTSD, or PTSD and comorbid substance use disorders, informed by our mouse model. Examine the genetics and epidemiology of substance abuse among men and women separately in a large military sample, informed by our mouse model
Keywords mouse model, stress vulnerability, TIA-1 SNPs
Date concluded 7/31/2016
Treatment Type n/a
Target population Mouse Studies
IND n/a
 
 
 
Oxytocin Suppresses Substance Use Disorders Associated with Chronic Stress
Principal Investigator(s): Jacqueline F. McGinty, Ph.D.
Lay Abstract Study/Product Aim(s): Demonstrate effects of systemic oxytocin or carbetocin administration on reinstatement of meth seeking and epigenetic adaptations in the brain of rats after chronic stress. Demonstrate effects of systemic oxytocin or carbetocin administration on reinstatement of ethanol seeking and epigenetic adaptations in the brain of mice after chronic stress. Demonstrate effects of intra-nasal oxytocin administration on PTSD symptoms and substance use of dual-diagnosed veterans.
Keywords animal studies, meth addiction, alcohol abuse, PTSD
Date concluded 6/30/2016
Treatment Type Pharmacological: Oxytocin (intranasal) & Carbetocin
Target population Rat Studies
IND This study has an active IND
 
 
 

Concluded Proof of Principle Projects funded by ITN

Topiramate Treatment of Hazardous and Harmful Alcohol Use in Veterans with TBI
Principal Investigator(s): Steven L. Batki, M.D.
Lay Abstract The project aims to: 1)Obtain a preliminary assessment of the effectiveness of topiramate in reducing alcohol use and TBI symptoms in veterans with TBI and hazardous or harmful alcohol use; 2)Assess the safety/tolerability of topiramate in these patients; 3)Assess the feasibility of recruitment/retention for topiramate treatment; and 4)To inform the design of a planned subsequent larger controlled trial of topiramate.
Keywords alcohol abuse, toprimate, mTBI, veterans, pharmacotherapy, co-occurring disorders, topiramate
Date concluded 10/31/2015
Treatment Type Pharmacologic: Toprimate
Target Population Veterans with TBI and AUD
IND exempt
 
 
 
Animal models of binge drinking and PTSD: novel therapeutic targets and pharmacological interventions from gene expression profiles
Principal Investigator(s): John C. Crabbe, Ph.D.
Lay Abstract Study/ProductAims: •Employ HDID binge drinking mice to test novel compounds for efficacy to reduce drinking •Provide brain tissue from HDID mice to Texas to discover novel compounds for testing •Use PTSD-like assay to exacerbate binge drinking in HDID mice
Keywords alcohol; binge drinking; posttraumatic stress disorder; genetics; pharmacotherapy
Date concluded 12/31/2013
Treatment Type Pharmacological: tezaglitazer, fenofibrate
Target Population Mouse Studies (HDID)
IND n/a
 
 
 
Catechol-O-Methyltransferase, Impulsivity and Substance Abuse Treatment
Lay Abstract Determine whether tolcapone will preferentially reduce impulsivity in individuals with the val/val 158 genotype and produce commensurate changes in CNS circuits involved in intertemporal choice. Determine whether entacapone will preferentially reduce impulsivity in individuals with the val/val 158 genotype and produce commensurate changes in CNS circuits involved in intertemporal choice. Determine whether the effect of COMT inhibitors on impulsivity depends upon their ability to cross the blood brain barrier.
Keywords tolcapone, impulsivity, COMT inhibitors
Date concluded 6/30/2016
Treatment Type Pharmacological: tolcapone & entacapone (COMT inhibitors)
Target Population Civilians
IND not required
 
 
 
Animal models of binge drinking and PTSD: novel therapeutic targets and pharmacological interventions from gene expression profiles
Principal Investigator(s): R. Adron Harris, Ph.D.
Lay Abstract The overall goal of this work is to combine genomic and behavioral approaches to repurpose approved medications that can provide new and effective treatments for combined binge drinking and PTSD
Keywords alcohol; binge drinking; posttraumatic stress disorder; genetics; pharmacotherapy
Date concluded 12/31/2013
Treatment Type Genetics studies looking for drug targets
Target Population Mouse and rat studies
IND n/a
 
 
 
Glial regulators for treating comorbid post-traumatic stress disorder (injury) and substance abuse disorders
Principal Investigator(s): Peter W. Kalivas, Ph.D.
Lay Abstract Study/Product Aim(s): • Establish a proof-of-concept clinical trial protocol for measuring drug craving and relapse in Veterans with comorbid PTSD and substance use disorders (SUDs). • Determine the efficacy and safety of N-acetylcysteine in preventing relapse and reducing drug craving and PTSD symptoms among Veterans with comorbid PTSD and SUDs. This comorbidity is currently not effectively treated.
Keywords PTSD. Glia, stress, plasticity, addiction, Prefrontal cortex, cocaine, N-actetylcysteine; glutamate
Date concluded 6/30/2014
Treatment Type Pharmacological: NAC
Target population Veterans (with PTSD/SUD)
IND no IND required
 
 
 
 
A translational epidemiological approach to the molecular basis of PTSD and substance abuse comorbidity
Principal Investigator(s): Eric R. Kandel, M.D.
Lay Abstract Study/Product Aim(s): • Identify causal biological mechanisms of PTSD using a novel gene x environment mouse model of stress vulnerability, and characterize the interaction between PTSD-like symptoms and nicotine/alcohol consumption • Identify SNPs associated with PTSD, or PTSD and comorbid substance use disorders, informed by our mouse model • Examine the epidemiology of substance abuse among men and women separately in a large military sample, informed by our mouse model
Keywords PTSD, substance use disorders, male and female military personnel, animal models, causal molecular mechanisms, gateway sequence, nicotine, alcohol
Date concluded 9/30/2013
Treatment Type n/a
Target population n/a
IND n/a
 
 
 
Development of an animal model & novel treatments for comorbid PTSD and cocaine addiction
Principal Investigator(s): Lori A. Knackstedt, Ph.D.
Lay Abstract

Aim 1. Will treatment with an AT1R antagonist or ACE inhibitor after a “traumatic event” prevent the expression of symptoms of PTSD? Aim 2. Will therapy with an AT1R blocker or ACE inhibitor reduce cocaine seeking in an animal model of comorbid PTSD and cocaine addiction? Aim 3: Will therapy with an AT1R blocker or ACE inhibitor reduce methamphetamine-seeking in an animal model of comorbid PTSD and methamphetamine addiction?

Keywords PTSD, Cocaine, Substance Use Disorder, Animal Model, Addiction, Angiotensin, Captoril, Candesartan
Date concluded 8/31/2016
Treatment Type Substance Abuse: Cocaine
Target population Rat Studies
IND n/a
 
 
 
 
Epigenetic modulation of interactions between fear and substance abuse
Principal Investigator(s): Kennon M. Lattal, Ph.D.
Lay Abstract Study/Product Aim(s): •To determine whether potentiation of extinction by an HDAC3 inhibitor in a rodent model of PTSD weakens the ability of cues associated with trauma to cause relapse of drug seeking. •To determine whether potentiation of extinction of drug seeking by an HDAC3 inhibitor protects extinguished drug seeking from reinstatement induced by cues associated with trauma.
Keywords substance abuse, fear conditioning, HDAC3 inhibitor, RGFP966, extinction of fear
Date concluded 9/30/2014
Treatment Type Pharmacologic: HDAC3 Inhibitor called RGFP966
Target population Mouse and rat studies
IND n/a
 
 
 
Endogenous Modulators Suppress Substance Abuse Disorders Associated with Chronic Stress
Principal Investigator(s): Jacqueline F. McGinty, Ph.D.
Lay Abstract Study/Product Aim(s): • Establish a preclinical model of PTSD vulnerability to methamphetamine (METH) self administration and seeking. • Demonstrate effects of oxytocin and carbetocin on reinstatement of meth seeking after chronic stress. • Examine neurobiological and epigenetic adaptations in the brains of METH seeking rats pre-exposed to chronic stress and treated with oxytocin or carbetocin.
Keywords Treatment Development
Date concluded 12/31/2013
Treatment Type Pharmacological: oxytocin
Target population PTSD model Rats studies
IND n/a
 
 
 
 
Oxytocin Suppresses Alcohol Drinking and Relapse in Mice
Principal Investigator(s): Jacqueline F. McGinty, Ph.D.
Lay Abstract Study/Product Aim(s): Determine the effects of oxytocin treatment on alcohol consumption in mice using a binge model of drinking. Determine the effects of oxytocin treatment on alcohol responding, consumption, and relapse behavior in mice.
Keywords oxytocin, binge-like alcohol drinking, mouse models, relapse
Date concluded 8/31/2015
Treatment Type Pharmacological: Oxytocin
Target population Mouse Studies
IND n/a
 
 
 
 
N-Type Calcium Channel Blockers for PTSD and Alcohol Use Disorders
Principal Investigator(s): Robert O. Messing, M.D.
Lay Abstract

Study/Product Aims ; 1. Determine if drugs that inhibit N-type calcium channels reduce PTSD-like behavior in rats. 2. Determine if inhibitors of N-type calcium channels reduce operant ethanol self-administration and stress-induced reinstatement of
ethanol seeking.

Keywords PTSD, alcohol abuse, rat studies, lomerizine, Z160, N-type Calcium channel blockers
Date concluded 6/30/2013
Treatment Type Pharmacological: Lomerizine & Z160
Target population Rat studies
IND n/a
 
 
 
Zonisamide and CPT for veterans with PTSD and comorbid alcohol dependence
Principal Investigator(s): Ismene L. Petrakis, M.D.
Lay Abstract Hypothesis: We hypothesize that zonisamide will be more effective than placebo when used in combination of E-CPT-C in 1.) reducing heavy drinking days measured by the Timeline Follow-back Method (TLFB) 2.) reducing drinks per week as measured by the Timeline Follow-back Method (TLFB), 3.) reducing craving for alcohol using the Obsessive Compulsive Drinking Scale (OCDS).
Keywords treatment, pharmacotherapy, alcohol dependence, PTSD, zonisamide, cognitive processing therapy, alcohol use disorders
Date concluded 6/30/2015
Treatment Type Pharmacologic and Cognitive Processing Therapy Combo: Zonisamide
Target population Veterans with PTSD and AUD
IND exempt
 
 
 
Heat Shock Protein 90 at the Intersection of Alcohol Abuse and Stress – Preclinical Studies
Principal Investigator(s): Dorit Ron, Ph.D.
Lay Abstract Study Aim: • Confirm our hypothesis stating that HSP90 is a focal shared contributor to mechanisms underlying alcohol abuse and stress • Test pharmacotherapies at the preclinical level to decrease stress-induced
Keywords alcohol abuse, alcohol relapse, HSP90 inhibitor, NVP-AUY922
Date concluded 6/30/2014
Treatment Type Pharmacologic: HSP90 inhibitor
Target population Rat studies
IND n/a
 
 
 
Role of extended amygdala corticotropin-releasing factor and dynorphin brain systems in post-trauma ethanol use disorders
Principal Investigator(s): Eric P. Zorrilla, Ph.D.
Lay Abstract Study/Product Aim(s) Task #1: To characterize post-stress and post-ethanol adverse ethanol use in the rat vis-à-vis compulsiveness and relapse. Task #2: To relate overactivation markers in CRF-CRF1 or dynorphin-KOR brain stress system to poor ethanol use outcomes Task #3: To inhibit CRF-CRF1 or dynorphin-KOR stress systems to reverse poor post-stress ethanol use outcomes.
Keywords PTSD, relapse, coticotropin-releasing factor, kappa opioid receptor, alcholism, ethanol reinforcement, dynophin, self-administration behavior
Date concluded 10/24/2014
Treatment Type Pharmacological: inhibition of the CRF-CRF1 or dynorphi-KOR stress systems (pexacerfont or CYM-50202)
Target population Rat studies
IND n/a