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Corticotropin releasing and addiction

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https://www.readbyqxmd.com/read/28319850/methylation-of-hpa-axis-related-genes-in-men-with-hypersexual-disorder
#1
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...
March 10, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28302012/targeting-npy-crf-ucns-and-nps-neuropeptide-systems-to-treat-alcohol-use-disorder-aud
#2
Francisco David 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...
March 16, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28265716/don-t-stress-about-crf-assessing-the-translational-failures-of-crf1antagonists
#3
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...
March 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28237884/effects-of-crack-cocaine-addiction-and-stress-related-genes-on-peripheral-bdnf-levels
#4
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...
February 11, 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
#5
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
#6
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...
January 3, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28028605/neuropeptide-systems-and-new-treatments-for-nicotine-addiction
#7
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...
December 28, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27837404/the-biology-of-addiction
#8
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
https://www.readbyqxmd.com/read/27809751/structure-and-function-of-small-non-peptide-crf-antagonists-and-their-potential-clinical-use
#9
Hesham Fahmy, Bahimanna Kuppast, Mohamed Teleb Ismail
Corticotropin-releasing factor (CRF) can be considered a very important hormone or a chemical mediator. It works closely with other systems to regulate the manner through which the body may respond to stress. Thus it affect many biological processes associated with stress. Dysfunction of this system has also been correlated with various diseases such as major depression, anxiety, drug addiction and eating disorders. Rationally, this means that interfering with binding of CRF to its intended receptors can be an attractive target for drug design aiming at developing new medications for many ailments that are associated with stress such as depression, anxiety and stress-induced relapse in drug addiction...
November 1, 2016: Current Molecular Pharmacology
https://www.readbyqxmd.com/read/27798128/a-functional-switch-in-tonic-gaba-currents-alters-the-output-of-central-amygdala-corticotropin-releasing-factor-receptor-1-neurons-following-chronic-ethanol-exposure
#10
Melissa A Herman, Candice Contet, Marisa Roberto
The corticotropin releasing factor (CRF) system in the central amygdala (CeA) has been implicated in the effects of acute ethanol and the development of alcohol dependence. We previously demonstrated that CRF receptor 1 (CRF1) neurons comprise a specific component of the CeA microcircuitry that is selectively engaged by acute ethanol. To investigate the impact of chronic ethanol exposure on inhibitory signaling in CRF1+ CeA neurons, we used CRF1:GFP mice subjected to chronic intermittent ethanol (CIE) inhalation and examined changes in local inhibitory control, the effects of acute ethanol, and the output of these neurons from the CeA...
October 19, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/27693397/selective-crf2-receptor-agonists-ameliorate-the-anxiety-and-depression-like-state-developed-during-chronic-nicotine-treatment-and-consequent-acute-withdrawal-in-mice
#11
Zsolt Bagosi, Miklós Palotai, Balázs Simon, Péter Bokor, András Buzás, Beáta Balangó, Dávid Pintér, Miklós Jászberényi, Krisztina Csabafi, Gyula Szabó
The aim of the present study was to investigate the effects of the selective agonists of the corticotropin-releasing factor (CRF) 2 receptor, urocortin 2 (UCN 2) and urocortin 3 (UCN 3), on the anxiety- and depression-like signs induced by acute nicotine withdrawal in mice. In order to do so, male CFLP mice were exposed for 7 days to repeated intraperitoneal (IP) injection with nicotine or saline solution and 1day of acute withdrawal and then a single intracerebroventricular (ICV) injection with UCN 2, UCN 3 or saline solution...
September 29, 2016: Brain Research
https://www.readbyqxmd.com/read/27612874/corticotropin-releasing-factor-receptors-and-their-interacting-proteins-functional-consequences
#12
Paula G Slater, Hector E Yarur, Katia Gysling
The corticotropin-releasing factor (CRF) system, which is involved in stress, addiction, and anxiety disorders such as depression, acts through G-protein-coupled receptors (GPCRs) known as type-1 and type-2 CRF receptors. The purpose of this review is to highlight recent advances in the interactions of CRF receptors with other GPCRs and non-GPCR proteins and their associated functional consequences. A better understanding of these interactions may generate new pharmacological alternatives for the treatment of addiction and stress-related disorders...
November 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27595147/effect-of-the-crf1-receptor-antagonist-pexacerfont-on-stress-induced-eating-and-food-craving
#13
David H Epstein, Ashley P Kennedy, Melody Furnari, Markus Heilig, Yavin Shaham, Karran A Phillips, Kenzie L Preston
RATIONALE: In rodents, antagonism of receptors for corticotropin-releasing factor (CRF) blocks stress-induced reinstatement of drug or palatable food seeking. OBJECTIVE: To test anticraving properties of the CRF1 antagonist pexacerfont in humans. METHODS: We studied stress-induced eating in people scoring high on dietary restraint (food preoccupation and chronic unsuccessful dieting) with body-mass index (BMI) >22. In a double-blind, between-groups trial, 31 "restrained" eaters were stabilized on either pexacerfont (300 mg/day for 7 days, then 100 mg/day for 21 days) or placebo...
September 5, 2016: Psychopharmacology
https://www.readbyqxmd.com/read/27475769/neurobiology-of-addiction-a-neurocircuitry-analysis
#14
REVIEW
George F Koob, Nora D Volkow
Drug addiction represents a dramatic dysregulation of motivational circuits that is caused by a combination of exaggerated incentive salience and habit formation, reward deficits and stress surfeits, and compromised executive function in three stages. The rewarding effects of drugs of abuse, development of incentive salience, and development of drug-seeking habits in the binge/intoxication stage involve changes in dopamine and opioid peptides in the basal ganglia. The increases in negative emotional states and dysphoric and stress-like responses in the withdrawal/negative affect stage involve decreases in the function of the dopamine component of the reward system and recruitment of brain stress neurotransmitters, such as corticotropin-releasing factor and dynorphin, in the neurocircuitry of the extended amygdala...
August 2016: Lancet Psychiatry
https://www.readbyqxmd.com/read/27374820/binge-drinking-decreases-corticotropin-releasing-factor-binding-protein-expression-in-the-medial-prefrontal-cortex-of-mice
#15
Kyle D Ketchesin, Gwen S Stinnett, Audrey F Seasholtz
BACKGROUND: Dysregulation of the corticotropin-releasing factor (CRF) system has been observed in rodent models of binge drinking, with a large focus on CRF receptor 1 (CRF-R1). The role of CRF-binding protein (CRF-BP), a key regulator of CRF activity, in binge drinking is less well understood. In humans, single-nucleotide polymorphisms in CRHBP are associated with alcohol use disorder and stress-induced alcohol craving, suggesting a role for CRF-BP in vulnerability to alcohol addiction...
August 2016: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/27053215/episodic-social-stress-escalated-cocaine-self-administration-role-of-phasic-and-tonic-corticotropin-releasing-factor-in-the-anterior-and-posterior-ventral-tegmental-area
#16
Elizabeth N Holly, Christopher O Boyson, Sandra Montagud-Romero, Dirson J Stein, Kyle L Gobrogge, Joseph F DeBold, Klaus A Miczek
UNLABELLED: Intermittent social defeat stress escalates later cocaine self-administration. Reward and stress both activate ventral tegmental area (VTA) dopamine neurons, increasing downstream extracellular dopamine concentration in the medial prefrontal cortex and nucleus accumbens. The stress neuropeptide corticotropin releasing factor (CRF) and its receptors (CRF-R1, CRF-R2) are located in the VTA and influence dopaminergic activity. These experiments explore how CRF release and the activation of its receptors within the VTA both during and after stress influence later cocaine self-administration in rats...
April 6, 2016: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/26907955/substance-use-modulates-stress-reactivity-behavioral-and-physiological-outcomes
#17
REVIEW
Anne Q Fosnocht, Lisa A Briand
Drug addiction is a major public health concern in the United States costing taxpayers billions in health care costs, lost productivity and law enforcement. However, the availability of effective treatment options remains limited. The development of novel therapeutics will not be possible without a better understanding of the addicted brain. Studies in both clinical and preclinical models indicate that chronic drug use leads to alterations in the body and brain's response to stress. Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis may shed light on the ability of stress to increase vulnerability to relapse...
November 1, 2016: Physiology & Behavior
https://www.readbyqxmd.com/read/26786746/alcohol-consumption-increases-locomotion-in-an-open-field-and-induces-fos-immunoreactivity-in-reward-and-approach-withdrawal-related-neurocircuitries
#18
Tatiana Wscieklica, Milena de Barros Viana, Luciana Le Sueur Maluf, Kathlein Cristiny Peres Pouza, Regina Célia Spadari, Isabel Cristina Céspedes
Drug addiction is a chronically relapsing disorder characterized by compulsion to seek and take the drug, loss of control in limiting intake and, eventually, the emergence of a negative emotional state when access to the drug is prevented. Both dopamine and corticotropin-releasing factor (CRF)-mediated systems seem to play important roles in the modulation of alcohol abuse and dependence. The present study investigated the effects of alcohol consumption on anxiety and locomotor parameters and on the activation of dopamine and CRF-innervated brain regions...
February 2016: Alcohol
https://www.readbyqxmd.com/read/26596556/antagonism-of-gaba-b-but-not-gaba-a-receptors-in-the-vta-prevents-stress-and-intra-vta-crf-induced-reinstatement-of-extinguished-cocaine-seeking-in-rats
#19
Jordan M Blacktop, Oliver Vranjkovic, Matthieu Mayer, Matthew Van Hoof, David A Baker, John R Mantsch
Stress-induced reinstatement of cocaine seeking requires corticotropin releasing factor (CRF) actions in the ventral tegmental area (VTA). However the mechanisms through which CRF regulates VTA function to promote cocaine use are not fully understood. Here we examined the role of GABAergic neurotransmission in the VTA mediated by GABA-A or GABA-B receptors in the reinstatement of extinguished cocaine seeking by a stressor, uncontrollable intermittent footshock, or bilateral intra-VTA administration of CRF. Rats underwent repeated daily cocaine self-administration (1...
March 2016: Neuropharmacology
https://www.readbyqxmd.com/read/26503565/corticotropin-releasing-factor-type-2-receptor-and-corticotropin-releasing-factor-binding-protein-coexist-in-rat-ventral-tegmental-area-nerve-terminals-originated-in-the-lateral-hypothalamic-area
#20
Paula G Slater, Veronica Noches, Katia Gysling
There is significant functional evidence showing that corticotropin-releasing factor type-2 receptor (CRF2R) and corticotropin-releasing factor-binding protein (CRF-BP) regulate glutamatergic synapses onto ventral tegmental area (VTA) dopaminergic neurons. It has been shown that CRF requires CRF-BP to potentiate N-methyl-D-aspartate receptors in dopaminergic neurons through CRF2R, and that increases glutamate release in cocaine-treated rats through the activation of CRF2R only by agonists with high affinity to CRF-BP...
January 2016: European Journal of Neuroscience
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