Dynorphin, Dysphoria, and Dependence: the Stress of Addiction

Chavkin, Charles; Koob, George F.

doi:10.1038/npp.2015.258

Cited by 131 publications

(87 citation statements)

References 6 publications

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“…As addiction progresses, upregulation of neural stress systems, including CRF, occurs in parallel with the downregulated neural reward systems (e.g., those in the basal ganglia), as described above (75), and some brain stress systems such as the dynorphin-kappa system may directly decrease reward function (76). For example, alcohol-dependent rats were more sensitive to CRF and CRF1 antagonists with respect to the increase and decrease, respectively of release of GABA in CeA interneurons (54).…”

Section: Stages Of the Addiction Cycle And The Addictions Neuroclimentioning

confidence: 99%

Addictions Neuroclinical Assessment: A reverse translational approach

et al. 2017

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Incentive salience, negative emotionality, and executive function are functional domains that are etiologic in the initiation and progression of addictive disorders, having been implicated in humans with addictive disorders and in animal models of addictions. Measures of these three neuroscience-based functional domains can capture much of the effects of inheritance and early exposures that lead to trait vulnerability shared across different addictive disorders. For specific addictive disorders, these measures can be supplemented by agent specific measures such as those that access pharmacodynamic and pharmacokinetic variation attributable to agent-specific gatekeeper molecules including receptors and drug-metabolizing enzymes. Herein, we focus on the translation and reverse translation of knowledge derived from animal models of addiction to the human condition via measures of neurobiological processes that are orthologous in animals and humans, and that are shared in addictions to different agents. Based on preclinical data and human studies, measures of these domains in a general framework of an Addictions Neuroclinical Assessment (ANA) can transform the assessment and nosology of addictive disorders, and can be informative for staging disease progression. We consider next steps and challenges for implementation of ANA in clinical care and research.

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Section: Stages Of the Addiction Cycle And The Addictions Neuroclimentioning

confidence: 99%

Addictions Neuroclinical Assessment: A reverse translational approach

et al. 2017

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“…They are activated by the endogenous release of neuropeptides derived from prodynorphin, and produce behavioral phenotypes indicative of negative emotional states such as place aversion and depressive-like affective behaviors [56]. The prominent neuromodulatory effect of KOP on the dopaminergic system is now the subject of clinical development, with the goal of removing opioid-induced protracted abstinence syndrome characterized by negative affect that can drive relapse.…”

Section: Allostatic Processes In the Vtamentioning

confidence: 99%

Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation

Cahill

Walwyn

Taylor

et al. 2016

Trends in Pharmacological Sciences

105

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Mechanisms of opioid tolerance have focused on adaptive modifications within cells containing opioid receptors, defined here as cellular allostasis, emphasizing regulation of the opioid receptor signalosome. We review additional regulatory and opponent processes involved in behavioral tolerance, and include mechanistic differences both between agonists (agonist bias), and between μ- and δ-opioid receptors. In a process we will refer to as pass-forward allostasis, cells modified directly by opioid drugs impute allostatic changes to downstream circuitry. Because of the broad distribution of opioid systems, every brain cell may be touched by pass-forward allostasis in the opioid-dependent/tolerant state. We will implicate neurons and microglia as interactive contributors to the cumulative allostatic processes creating analgesic and hedonic tolerance to opioid drugs.

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“…The main focus in this mini-review is several other important stress responsive systems, which recently has not been reviewed, like arginine vasopressin/V1b receptors (Part I), and proopiomelanocortin/β-endorphin (Part II). Also, in other two stress responsive systems, endocannabinoids/fatty acid amide hydrolase [Part III], and dynorphin/kappa opioid receptors [Part IV], we examine possible explanations for the controversy in the literature, to assess the most current state of the field [Parsons and Hurd, 2015;Chavkin and Koob, 2016;Anderson and Becker, 2017;Karkhanis et al, 2017;Tunstall et al, 2017]. Therefore, this mini-review will provide an overview of the recent literature on the above four stress responsive systems in alcohol research, using laboratory based animal models and clinical research to elucidate the biology of addictive diseases.…”

Section: Introductionmentioning

confidence: 99%

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

Zhou

Kreek

2018

J Pharmacol Exp Ther

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Addiction to specific drugs (such as alcohol, psychostimulants and opioids) shares some common direct or downstream effects on the brain stress-responsive systems, including arginine vasopressin and its V1b receptors, dynorphin and the kappa opioid receptors, proopiomelanocortin/β-endorphin and the mu opioid receptors, and the endocannabinoids. Further study of these systems, through laboratory-based and translational research, could lead to the discovery of novel treatment targets and the early optimization of interventions (for example, combination) for the pharmacological therapy of alcoholism.

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Dynorphin, Dysphoria, and Dependence: the Stress of Addiction

Cited by 131 publications

References 6 publications

Addictions Neuroclinical Assessment: A reverse translational approach

Addictions Neuroclinical Assessment: A reverse translational approach

Allostatic Mechanisms of Opioid Tolerance Beyond Desensitization and Downregulation

Involvement of Activated Brain Stress Responsive Systems in Excessive and “Relapse” Alcohol Drinking in Rodent Models: Implications for Therapeutics

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