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Corticotropin releasing and addiction

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
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
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
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
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
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
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...
February 18, 2016: Physiology & Behavior
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
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
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
Almudena Gómez-Román, Juan A Ortega-Sánchez, David Rotllant, Humberto Gagliano, Xavier Belda, Raúl Delgado-Morales, Ignacio Marín-Blasco, Roser Nadal, Antonio Armario
There have been numerous studies into the interaction between stress and addictive drugs, yet few have specifically addressed how the organism responds to stress when under the influence of psychostimulants. Thus, we studied the effects of different acute stressors (immobilization, interleukin-1β and forced swimming) in young adult male rats simultaneously exposed to amphetamine (AMPH, 4 mg/kg SC), evaluating classic biological markers. AMPH administration itself augmented the plasma hypothalamic-pituitary-adrenal (HPA) hormones, adrenocorticotropin (ACTH) and corticosterone, without affecting plasma glucose levels...
January 2016: Psychoneuroendocrinology
Maenghee Kang-Park, Brigitte L Kieffer, Amanda J Roberts, George R Siggins, Scott D Moore
The corticotropin-releasing factor (CRF) and kappa-opioid receptor (KOR) systems are both implicated in stress-related behaviors and drug dependence. Although previous studies suggest that antagonism of each system blocks aspects of experimental models of drug dependence, the possible interaction between these systems at the neuronal level has not been completely examined. We used an in vitro brain slice preparation to investigate the interaction of these two peptide systems on inhibitory neurotransmission in the central nucleus of the amygdala (CeA)...
November 2015: Journal of Pharmacology and Experimental Therapeutics
Juan-Antonio García-Carmona, Daymi M Camejo, Pilar Almela, Ana Jiménez, María-Victoria Milanés, Francisca Sevilla, María-Luisa Laorden
Corticotropin-releasing factor (CRF) acts as neuro-regulator of the behavioral and emotional integration of environmental and endogenous stimuli associated with drug dependence. Thioredoxin-1 (Trx-1) is a functional protein controlling the redox status of several proteins, which is involved in addictive processes. In the present study, we have evaluated the role of CRF1 receptor (CRF1R) in the rewarding properties of morphine by using the conditioned place preference (CPP) paradigm. We also investigate the effects of the CRF1R antagonist, CP-154,526, on the morphine CPP-induced activation of CRF neurons, CREB phosphorylation and Trx expression in paraventricular nucleus (PVN) and dentate gyrus (DG) of the mice brain...
2015: PloS One
Edmilson D Dos Santos Júnior, André V Da Silva, Kelly R T Da Silva, Carlos A S Haemmerle, Daniella S Batagello, Joelcimar M Da Silva, Leandro B Lima, Renata J Da Silva, Giovanne B Diniz, Luciane V Sita, Carol F Elias, Jackson C Bittencourt
The oculomotor accessory nucleus, often referred to as the Edinger-Westphal nucleus [EW], was first identified in the 17th century. Although its most well known function is the control of pupil diameter, some controversy has arisen regarding the exact location of these preganglionic neurons. Currently, the EW is thought to consist of two different parts. The first part [termed the preganglionic EW-EWpg], which controls lens accommodation, choroidal blood flow and pupillary constriction, primarily consists of cholinergic cells that project to the ciliary ganglion...
October 2015: Journal of Chemical Neuroanatomy
Dana M LeBlanc, M Adrienne McGinn, Christy A Itoga, Scott Edwards
Addiction, or substance use disorder (SUD), is a devastating psychiatric disease composed of multiple elemental features. As a biobehavioral disorder, escalation of drug and/or alcohol intake is both a cause and consequence of molecular neuroadaptations in central brain reinforcement circuitry. Multiple mesolimbic areas mediate a host of negative affective and motivational symptoms that appear to be central to the addiction process. Brain stress- and reinforcement-related regions such as the central amygdala (CeA), prefrontal cortex (PFC), and nucleus accumbens (NAc) also serve as central processors of ascending nociceptive input...
December 2015: Alcohol
John R Mantsch, David A Baker, Douglas Funk, Anh D Lê, Yavin Shaham
In human addicts, drug relapse and craving are often provoked by stress. Since 1995, this clinical scenario has been studied using a rat model of stress-induced reinstatement of drug seeking. Here, we first discuss the generality of stress-induced reinstatement to different drugs of abuse, different stressors, and different behavioral procedures. We also discuss neuropharmacological mechanisms, and brain areas and circuits controlling stress-induced reinstatement of drug seeking. We conclude by discussing results from translational human laboratory studies and clinical trials that were inspired by results from rat studies on stress-induced reinstatement...
January 2016: Neuropsychopharmacology: Official Publication of the American College of Neuropsychopharmacology
Juan-Antonio García-Carmona, Alberto Baroja-Mazo, María-Victoria Milanés, María Luisa Laorden
BACKGROUND: Extinction period of positive affective memory of drug taking and negative affective memory of drug withdrawal, as well as the different response of men and women might be important for the clinical treatment of drug addiction. We investigate the role of corticotropin releasing factor receptor type one (CRF1R) and the different response of male and female mice in the expression and extinction of the aversive memory. METHODOLOGY/PRINCIPAL FINDING: We used genetically engineered male and female mice lacking functional CRF1R...
2015: PloS One
Xiujun Tang, Shumin Zhan, Liping Yang, Wenyan Cui, Jennie Z Ma, Thomas J Payne, Ming D Li
Twin and family studies indicate that smoking addiction is highly influenced by genetic factors. Variants in the corticotropin-releasing hormone receptor 1 (CRHR1) gene have been associated with alcoholism and depression. In this study, we tested five single nucleotide polymorphisms (SNPs) in CRHR1 for their association with ND, which was assessed by smoking quantity (SQ), the Heaviness of Smoking Index (HSI), and the Fagerström test for ND (FTND) in 2,037 subjects from 602 families of either European American (EA) or African American (AA) ancestry...
2015: BioMed Research International
Yuval Silberman, Danny G Winder
The central amygdala is a critical brain region for many aspects of alcohol dependence. Much of the work examining the mechanisms by which the central amygdala mediates the development of alcohol dependence has focused on the interaction of acute and chronic ethanol with central amygdala corticotropin releasing factor signaling. This work has led to a great deal of success in furthering the general understanding of central amygdala neurocircuitry and its role in alcohol dependence. Much of this work has primarily focused on the hypothesis that ethanol utilizes endogenous corticotropin releasing factor signaling to upregulate inhibitory GABAergic transmission in the central amygdala...
May 2015: Alcohol
Jessica R Barson, Sarah F Leibowitz
The hypothalamus is now known to regulate alcohol intake in addition to its established role in food intake, in part through neuromodulatory neurochemicals termed neuropeptides. Certain orexigenic neuropeptides act in the hypothalamus to promote alcohol drinking, although they affect different aspects of the drinking response. These neuropeptides, which include galanin, the endogenous opioid enkephalin, and orexin/hypocretin, appear to stimulate alcohol intake not only through mechanisms that promote food intake but also by enhancing reward and reinforcement from alcohol...
February 4, 2016: Progress in Neuro-psychopharmacology & Biological Psychiatry
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