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Corticotropin releasing and addiction

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https://www.readbyqxmd.com/read/29231765/imaging-corticotropin-releasing-factor-and-nociceptin-in-addiction-and-ptsd-models
#1
Savannah Tollefson, Michael Himes, Rajesh Narendran
Addiction is composed of three phases: intoxication, withdrawal, and craving. Negative reinforcement, strengthening a behaviour by removing an aversive stimulus, has been associated with the withdrawal phase. An imbalance of neurotransmitters within the brain's stress (nociceptin, neuropeptide Y) and anti-stress (CRF, norepinephrine, etc.) system is attributed to negatively reinforced compulsive behaviours associated with relapse. Similarly, post-traumatic stress disorder is characterized by an overactive stress system...
December 12, 2017: International Review of Psychiatry
https://www.readbyqxmd.com/read/29082267/intermittent-access-to-ethanol-induces-escalated-alcohol-consumption-in-primates
#2
S G Lindell, M L Schwandt, S J Suomi, K C Rice, M Heilig, C S Barr
BACKGROUND: Escalation of voluntary alcohol drinking is characteristic of alcohol addiction and can be induced in rodents using intermittent access to alcohol. This model has been used to evaluate candidate therapeutics, but key systems involved in the transition into alcohol addiction, such as CRF, differ in their organization between rodents and primates. We examined the ability of an intermittent access schedule to induce escalation of voluntary alcohol drinking in non-human primates and used this model to assess the role of corticotropin releasing hormone (CRF) signaling in this process...
April 2017: Journal of Addictive Behaviors, Therapy & Rehabilitation
https://www.readbyqxmd.com/read/29066956/cell-type-specific-expression-of-corticotropin-releasing-hormone-binding-protein-in-gabaergic-interneurons-in-the-prefrontal-cortex
#3
Kyle D Ketchesin, Nicholas S Huang, Audrey F Seasholtz
Corticotropin-releasing hormone-binding protein (CRH-BP) is a secreted glycoprotein that binds CRH with very high affinity to modulate CRH receptor activity. CRH-BP is widely expressed throughout the brain, with particularly high expression in regions such as the amygdala, hippocampus, ventral tegmental area and prefrontal cortex (PFC). Recent studies suggest a role for CRH-BP in stress-related psychiatric disorders and addiction, with the PFC being a potential site of interest. However, the molecular phenotype of CRH-BP-expressing cells in this region has not been well-characterized...
2017: Frontiers in Neuroanatomy
https://www.readbyqxmd.com/read/29056155/corticotropin-releasing-factor-crf-and-addictive-behaviors
#4
Marisa Roberto, Samantha R Spierling, Dean Kirson, Eric P Zorrilla
Drug addiction is a complex disorder that is characterized by compulsivity to seek and take the drug, loss of control in limiting intake of the drug, and emergence of a withdrawal syndrome in the absence of the drug. The transition from casual drug use to dependence is mediated by changes in reward and brain stress functions and has been linked to a shift from positive reinforcement to negative reinforcement. The recruitment of brain stress systems mediates the negative emotional state produced by dependence that drives drug seeking through negative reinforcement mechanisms, defined as the "dark side" of addiction...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/29056150/substance-p-and-the-neurokinin-1-receptor-the-new-crf
#5
Jesse R Schank, Markus Heilig
Substance P (SP) is an 11-amino acid neuropeptide of the tachykinin family that preferentially activates the neurokinin-1 receptor (NK1R). First isolated 85 years ago and sequenced 40 years later, SP has been extensively studied. Early studies identified a role for SP and the NK1R in contraction of intestinal smooth muscle, central pain processing, and neurogenic inflammation. An FDA-approved NK1R antagonist, aprepitant, is used clinically for the treatment of chemotherapy-induced nausea, as the NK1R influences the activity of the brain stem emesis centers...
2017: International Review of Neurobiology
https://www.readbyqxmd.com/read/28842817/methamphetamine-induces-tet1-and-tet3-dependent-dna-hydroxymethylation-of-crh-and-avp-genes-in-the-rat-nucleus-accumbens
#6
Subramaniam Jayanthi, Betina Gonzalez, Michael T McCoy, Bruce Ladenheim, Veronica Bisagno, Jean Lud Cadet
Methamphetamine (METH) addiction is a biopsychosocial disorder that is accompanied by multiple relapses even after prolonged abstinence, suggesting the possibilities of long-lasting maladaptive epigenetic changes in the brain. Here, we show that METH administration produced time-dependent increases in the expression of corticotropin-releasing hormone (Crh/Crf), arginine vasopressin (Avp), and cocaine- and amphetamine-regulated transcript prepropeptide (Cartpt) mRNAs in the rat nucleus accumbens (NAc). Chromatin immunoprecipitation (ChIP) assays revealed that METH increased the abundance of phosphorylated CREB (pCREB) at the promoter of Cartpt but not at Avp or Crh DNA sequences...
August 25, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28750312/synthesis-of-2-imino-and-2-hydrazono-thiazolo-4-5-d-pyrimidines-as-corticotropin-releasing-factor-crf-antagonists
#7
Mohamed Teleb, Bhimanna Kuppast, Katerina Spyridaki, George Liapakis, Hesham Fahmy
Corticotropin-releasing factor (CRF) is an important neuropeptide hormone which controls the body's overall response to stress. It plays a crucial role in regulating the behavioral, cardiovascular, immune and gastrointestinal systems. Over-activation of the CRF system has been implicated in many disorders including anxiety, depression, drug addiction, hypertension, Irritable Bowel Syndrome (IBS), peptic ulcers, inflammation and others. Thus, binding of CRF to its receptors is an attractive target to develop new medications which aim at treating ailments associated with chronic stress...
September 29, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28639210/-oxytocin-and-the-mechanisms-of-alcohol-dependence
#8
REVIEW
Till Faehrmann, Gerald Zernig, Sergei Mechtcheriakov
One of the crucial purposes of treating alcohol-dependent patients is to enhance their ability to stay abstinent after detoxification therapy. Anxiety and stress vulnerability are the main factors provoking alcohol craving and relapse. In the first months of abstinence, alcohol-dependent patients frequently show sleep disturbances, irritability and depression, indicating chronic activation of stress pathways. In addition, the loss of confidence in interpersonal interactions results in social withdrawal and reduced willingness to participate in therapeutic programs...
June 21, 2017: Neuropsychiatrie: Klinik, Diagnostik, Therapie und Rehabilitation
https://www.readbyqxmd.com/read/28499100/probing-for-neuroadaptations-to-unpredictable-stressors-in-addiction-translational-methods-and-emerging-evidence
#9
Jesse T Kaye, Daniel E Bradford, Katherine P Magruder, John J Curtin
Stressors clearly contribute to addiction etiology and relapse in humans, but our understanding of specific mechanisms remains limited. Rodent models of addiction offer the power, flexibility, and precision necessary to delineate the causal role and specific mechanisms through which stressors influence alcohol and other drug use. This review describes a program of research using startle potentiation to unpredictable stressors that is well positioned to translate between animal models and clinical research with humans on stress neuroadaptations in addiction...
May 2017: Journal of Studies on Alcohol and Drugs
https://www.readbyqxmd.com/read/28442370/modulation-of-drug-choice-by-extended-drug-access-and-withdrawal-in-rhesus-monkeys-implications-for-negative-reinforcement-as-a-driver-of-addiction-and-target-for-medications-development
#10
REVIEW
S Stevens Negus, Matthew L Banks
Chronic drug exposure is hypothesized to recruit negative reinforcement processes that increase the magnitude and alter the mechanisms of drug reinforcement. Candidate substrates of negative reinforcement include increased signaling via stress-related neurotransmitters such as corticotropin releasing factor (CRF, acting at CRF receptors) or dynorphin (acting at kappa opioid receptors) and/or decreased signaling via reward-related neurotransmitters such as dopamine. Determinants of drug reinforcement can be examined with choice procedures, in which subjects choose between a drug of interest (e...
April 22, 2017: Pharmacology, Biochemistry, and Behavior
https://www.readbyqxmd.com/read/28436309/corticotropin-releasing-hormone-binding-protein-and-stress-from-invertebrates-to-humans
#11
Kyle D Ketchesin, Gwen S Stinnett, Audrey F Seasholtz
Corticotropin-releasing hormone (CRH) is a key regulator of the stress response. This peptide controls the hypothalamic-pituitary-adrenal (HPA) axis as well as a variety of behavioral and autonomic stress responses via the two CRH receptors, CRH-R1 and CRH-R2. The CRH system also includes an evolutionarily conserved CRH-binding protein (CRH-BP), a secreted glycoprotein that binds CRH with subnanomolar affinity to modulate CRH receptor activity. In this review, we discuss the current literature on CRH-BP and stress across multiple species, from insects to humans...
May 18, 2017: Stress: the International Journal on the Biology of Stress
https://www.readbyqxmd.com/read/28431971/influence-of-stress-associated-with-chronic-alcohol-exposure-on-drinking
#12
REVIEW
Howard C Becker
Stress is commonly regarded as an important trigger for relapse and a significant factor that promotes increased motivation to drink in some individuals. However, the relationship between stress and alcohol is complex, likely changing in form during the transition from early moderated alcohol use to more heavy uncontrolled alcohol intake. A growing body of evidence indicates that prolonged excessive alcohol consumption serves as a potent stressor, producing persistent dysregulation of brain reward and stress systems beyond normal homeostatic limits...
August 1, 2017: Neuropharmacology
https://www.readbyqxmd.com/read/28319850/methylation-of-hpa-axis-related-genes-in-men-with-hypersexual-disorder
#13
Jussi Jokinen, Adrian E Boström, Andreas Chatzittofis, Diana M Ciuculete, Katarina Görts Öberg, John N Flanagan, Stefan Arver, Helgi B Schiöth
Hypersexual Disorder (HD) defined as non-paraphilic sexual desire disorder with components of compulsivity, impulsivity and behavioral addiction, and proposed as a diagnosis in the DSM 5, shares some overlapping features with substance use disorder including common neurotransmitter systems and dysregulated hypothalamic-pituitary-adrenal (HPA) axis function. In this study, comprising 67 HD male patients and 39 male healthy volunteers, we aimed to identify HPA-axis coupled CpG-sites, in which modifications of the epigenetic profile are associated with hypersexuality...
June 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28302012/targeting-npy-crf-ucns-and-nps-neuropeptide-systems-to-treat-alcohol-use-disorder-aud
#14
REVIEW
Francisco D Rodriguez, Rafael Coveñas
BACKGROUND: The term Alcohol Use Disorder (AUD) incorporates different states of disease related to the recurrent use of alcohol and linked to the relevant impairment, disability and failure to perform major responsibilities in different realms. Many neurotransmitter systems are involved in the phases or states of alcoholism from reward mechanisms, associated to binge intoxication, to stress and anxiety linked to relapse and withdrawal. Some neuropeptides play a key function in the control of anxiety and stress, and establish a close relationship with the pathological mechanisms underlying alcohol addiction...
2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28265716/don-t-stress-about-crf-assessing-the-translational-failures-of-crf1antagonists
#15
REVIEW
Samantha R Spierling, Eric P Zorrilla
BACKGROUND: Dr. Athina Markou sought treatments for a common neural substrate shared by depression and drug dependence. Antagonists of corticotropin-releasing factor (CRF) receptors, a target of interest to her, have not reached the clinic despite strong preclinical rationale and sustained translational efforts. METHODS: We explore potential causes for the failure of CRF1 antagonists and review recent findings concerning CRF-CRF1 systems in psychopathology. RESULTS: Potential causes for negative outcomes include (1) poor safety and efficacy of initial drug candidates due to bad pharmacokinetic and physicochemical properties, (2) specificity problems with preclinical screens, (3) the acute nature of screens vs...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28237884/effects-of-crack-cocaine-addiction-and-stress-related-genes-on-peripheral-bdnf-levels
#16
Diego L Rovaris, Jaqueline B Schuch, Rodrigo Grassi-Oliveira, Breno Sanvicente-Vieira, Bruna S da Silva, Consuelo Walss-Bass, Diana Müller, Anderson R Stolf, Lisia von Diemen, Keila M M Ceresér, Thiago G Pianca, Claudia M Szobot, Felix H P Kessler, Tatiana Roman, Claiton H D Bau
This study examined the effects of glucocorticoid receptor (NR3C1), corticotropin-releasing hormone receptor 1 (CRHR1), and brain-derived neurotrophic factor (BDNF) genes on susceptibility to crack cocaine addiction and BDNF levels. Crack addicted patients who sought treatment (n = 280) and non-addicted individuals (n = 241) were assessed. Three SNPs in NR3C1 (rs6198, rs41423247, and rs10052957), three in CRHR1 (rs12944712, rs110402, and rs878886), and one in BDNF (rs6265) were genotyped. No significant effect was seen in the case-control analyses...
July 2017: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28223925/effects-of-intermittent-alcohol-exposure-on-emotion-and-cognition-a-potential-role-for-the-endogenous-cannabinoid-system-and-neuroinflammation
#17
Laura Sanchez-Marin, Francisco J Pavon, Juan Decara, Juan Suarez, Ana Gavito, Estela Castilla-Ortega, Fernando Rodriguez de Fonseca, Antonia Serrano
Intermittent alcohol exposure is a common pattern of adolescent alcohol use that can lead to binge drinking episodes. Alcohol use is known to modulate the endocannabinoid system (ECS), which is involved in neuronal communication, neuroplasticity, neuroinflammation and behavior. Adolescent male Wistar rats were exposed to 4-week intermittent alcohol intoxication (3 g/kg injections for 4 days/week) or saline (N = 12 per group). After alcohol deprivation, adult rats were assessed for emotionality and cognition and the gene expression of the ECS and other factors related to behavior and neuroinflammation was examined in the brain...
2017: Frontiers in Behavioral Neuroscience
https://www.readbyqxmd.com/read/28050629/antireward-compulsivity-and-addiction-seminal-contributions-of-dr-athina-markou-to-motivational-dysregulation-in-addiction
#18
REVIEW
George F Koob
RATIONALE AND OBJECTIVES: Addiction is defined as a chronically relapsing disorder characterized by compulsive drug seeking that is hypothesized to derive from multiple sources of motivational dysregulation. METHODS AND RESULTS: Dr. Athina Markou made seminal contributions to our understanding of the neurobiology of addiction with her studies on the dysregulation of reward function using animal models with construct validity. Repeated overstimulation of the reward systems with drugs of abuse decreases reward function, characterized by brain stimulation reward and presumbably reflecting dysphoria-like states...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#19
REVIEW
Adriaan W Bruijnzeel
RATIONALE: The mildly euphoric and cognitive enhancing effects of nicotine play a role in the initiation of smoking, while dysphoria and anxiety associated with smoking cessation contribute to relapse. After the acute withdrawal phase, smoking cues, a few cigarettes (i.e., lapse), and stressors can cause relapse. Human and animal studies have shown that neuropeptides play a critical role in nicotine addiction. OBJECTIVES: The goal of this paper is to describe the role of neuropeptide systems in the initiation of nicotine intake, nicotine withdrawal, and the reinstatement of extinguished nicotine seeking...
May 2017: Psychopharmacology
https://www.readbyqxmd.com/read/27837404/the-biology-of-addiction
#20
REVIEW
Brent MacNicol
In this narrative review, the neurobiological mechanisms underlying substance abuse and addiction are discussed with a particular emphasis on the mechanisms that promote ongoing use and relapse. Addiction is estimated to affect 10-15% or more of the adult population, including physicians. Genetic predisposition, psychological and environmental risk factors, the timing of exposure to the substance, the type of substance used, and the frequency of use influence the individual's susceptibility to addiction. Abused substances act on the brain's reward system, a neural circuit that produces pleasurable feelings in response to stimuli that promote survival, thereby modifying future behavior to seek out similar stimuli...
February 2017: Canadian Journal of Anaesthesia, Journal Canadien D'anesthésie
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