Pharmacologic management of comorbid post-traumatic stress disorder and addictions

Shorter, Daryl; Hsieh, John; Kosten, Thomas R.

doi:10.1111/ajad.12306

Cited by 54 publications

(42 citation statements)

References 68 publications

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“…Depending on the specific rodent drug self-administration paradigm used, specific features of human drug abuse can be evaluated (Panlilio et al, 2005; Sughondhabirom et al, 2005; Panlilio and Goldberg, 2007). Although it has been established that repeated cocaine consumption triggers long-lasting changes in brain plasticity, which contribute to drug craving during abstinence and might induce relapse into cocaine-seeking behavior, we still have a very limited understanding of the exact molecular changes in the brain, which is reflected by the poor success in developing efficient drugs for cocaine addiction (Shorter et al, 2015; Wolf, 2016). To increase our understanding of the changes taking place in the striatum from the first CSA to chronic CSA through CSA withdrawal, we studied the progression of mGluR 1/5 responses in striatal slices.…”

Section: Discussionmentioning

confidence: 99%

“…Cocaine addiction is a complex multifaceted condition, which thus far has impeded the development of efficient pharmacological treatment options (Shorter et al, 2015; Wolf, 2016). Repeated cocaine consumption decreases expression of metabotropic glutamate 5 receptors (mGluR 5 ) in the striatum, a subcortical region critical in mediating the effects of drugs of abuse (Ghasemzadeh et al, 2009; Knackstedt et al, 2010; Martinez et al, 2014; Milella et al, 2014; Pomierny-Chamiolo et al, 2015; Terbeck et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

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Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Hoffmann

Crouzin

Moreno

et al. 2016

IJNPPY

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Background:Cocaine addiction continues to be a major heath concern, and despite public health intervention there is a lack of efficient pharmacological treatment options. A newly identified potential target are the group I metabotropic glutamate receptors, with allosteric modulators showing particular promise.Methods:We evaluated the capacity of group I metabotropic glutamate receptors to induce functional responses in ex vivo striatal slices from rats with (1) acute cocaine self-administration, (2) chronic cocaine self-administration, and (3) 60 days cocaine self-administration withdrawal by Western blot and extracellular recordings of synaptic transmission.Results:We found that striatal group I metabotropic glutamate receptors are the principal mediator of the mGluR1/5 agonist (RS)-3,5-dihydroxyphenylglycine-induced cAMP responsive-element binding protein phosphorylation. Both acute and chronic cocaine self-administration blunted group I metabotropic glutamate receptor effects on cAMP responsive-element binding protein phosphorylation in the striatum, which correlated with the capacity to induce long-term depression, an effect that was maintained 60 days after chronic cocaine self-administration withdrawal. In the nucleus accumbens, the principal brain region mediating the rewarding effects of drugs, chronic cocaine self-administration blunted group I metabotropic glutamate receptor stimulation of extracellular signal-regulated protein kinases 1/2 and cAMP responsive-element binding protein. Interestingly, the group I metabotropic glutamate receptor antagonist/inverse-agonist, 2-methyl-6-(phenylethynyl)pyridine hydrochloride, led to a specific increase in cAMP responsive-element binding protein phosphorylation after chronic cocaine self-administration, specifically in the nucleus accumbens, but not in the striatum.Conclusions:Prolonged cocaine self-administration, through withdrawal, leads to a blunting of group I metabotropic glutamate receptor responses in the striatum. In addition, specifically in the accumbens, group I metabotropic glutamate receptor signaling to cAMP responsive-element binding protein shifts from an agonist-induced to an antagonist-induced cAMP responsive-element binding protein phosphorylation.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Hoffmann

Crouzin

Moreno

et al. 2016

IJNPPY

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“…Other studies have reported that the lifetime prevalence of any substance-use disorder (SUD) was twice as high in persons with PTSD vs. those not suffering from this disorder (Shorter et al 2015) and that alcohol is the most commonly abused drug in PTSD patients (Jacobsen et al 2001). Indeed, a recent study examined the relationship between the frequency of childhood physical, sexual and emotional abuse and the development of substance use and PTSD in an urban, civilian population.…”

Section: Epidemiology Of Comorbid Ptsd and Audmentioning

confidence: 99%

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Gilpin

Weiner

2016

Genes Brain and Behavior

127

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Post-traumatic stress disorder (PTSD) and alcohol-use disorder (AUD) are highly comorbid in humans. Although we have some understanding of the structural and functional brain changes that define each of these disorders, and how those changes contribute to the behavioral symptoms that define them, little is known about the neurobiology of comorbid PTSD and AUD, which may be due in part to a scarcity of adequate animal models for examining this research question. The goal of this review is to summarize the current state-of-the-science on comorbid PTSD and AUD. We summarize epidemiological data documenting the prevalence of this comorbidity, review what is known about the potential neurobiological basis for the frequent co-occurrence of PTSD and AUD and discuss successes and failures of past and current treatment strategies. We also review animal models that aim to examine comorbid PTSD and AUD, highlighting where the models parallel the human condition, and we discuss the strengths and weaknesses of each model. We conclude by discussing key gaps in our knowledge and strategies for addressing them: in particular, we (1) highlight the need for better animal models of the comorbid condition and better clinical trial design, (2) emphasize the need for examination of subpopulation effects and individual differences and (3) urge cross-talk between basic and clinical researchers that is reflected in collaborative work with forward and reverse translational impact.

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“…Summarizing this literature can inform researchers and clinicians about effective treatments, future research directions, and may offer insight into underlying mechanisms that can be studied preclinically in a bench to bedside and back approach. While several previous reviews of pharmacologic management have been conducted (Norman et al., ; Ralevski et al., ; Shorter et al., ; Sofuoglu et al., ), this review represents a comprehensive critical review that also extends previous work by including several randomized controlled trials (RCTs) that have been very recently published (Batki et al., ; Hien et al., ; Petrakis et al., ; Simpson et al., ).…”

mentioning

confidence: 92%

Posttraumatic Stress Disorder and Alcohol Use Disorder: A Critical Review of Pharmacologic Treatments

Petrakis

Simpson

2017

Alcoholism Clin & Exp Res

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Treatment of alcohol use disorder (AUD) is complicated by the presence of psychiatric comorbidity including posttraumatic stress disorder (PTSD). This is a critical review of the literature to date on pharmacotherapy treatments of AUD and PTSD. A systematic literature search using PubMed MESH terms for alcohol and substance use disorders, PTSD, and treatment was undertaken to identify relevant randomized clinical trials (RCTs). The studies were independently evaluated (IP and TS) and those that evaluated the efficacy of a pharmacotherapy for individuals diagnosed with AUD and PTSD and were randomized controlled trials (RCT) were selected. Studies were grouped in three categories: (1) those that evaluated first line treatments for PTSD, (2) those that evaluated medications to target AUD and (3) those that evaluated medications hypothesized to be effective in targeting alcohol consumption as well as PTSD symptoms. Nine RCTs were identified; three focused on medications to treat PTSD, four focused on AUD, and three to target both. One study included both a medication to treat PTSD and one to treat AUD so was discussed twice. All but one of the studies found that PTSD symptoms and drinking outcomes improved significantly over time. There is not one agent with clear evidence of efficacy in this comorbid group. The results for medications to treat PTSD are inconclusive because of contradictory results. There was weak evidence to support the use of medications to treat AUD among those with comorbidity with PTSD. Findings for medications that were hypothesized to treat both disorders were also contradictory. Most studies provided a combination of interventions to treat both disorders. Despite the contradictory results, this review suggests that individuals with AUD and comorbid PTSD can safely be prescribed medications used in non-comorbid populations and patients improve with treatment.

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Pharmacologic management of comorbid post-traumatic stress disorder and addictions

Cited by 54 publications

References 68 publications

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Posttraumatic Stress Disorder and Alcohol Use Disorder: A Critical Review of Pharmacologic Treatments

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Pharmacologic management of comorbid post-traumatic stress disorder and addictions

Cited by 54 publications

References 68 publications

Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Long-Lasting Impairment of mGluR5-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Neurobiology of comorbid post‐traumatic stress disorder and alcohol‐use disorder

Posttraumatic Stress Disorder and Alcohol Use Disorder: A Critical Review of Pharmacologic Treatments

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Product

Resources

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Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration

Long-Lasting Impairment of mGluR₅-Activated Intracellular Pathways in the Striatum After Withdrawal of Cocaine Self-Administration