The Experts below are selected from a list of 28062 Experts worldwide ranked by ideXlab platform
George F. Koob - One of the best experts on this subject based on the ideXlab platform.
-
corticotropin releasing Factor a key role in the neurobiology of addiction
Frontiers in Neuroendocrinology, 2014Co-Authors: Eric P. Zorrilla, Marian L Logrip, George F. KoobAbstract:Abstract Drug addiction is a chronically relapsing disorder characterized by loss of control over intake and dysregulation of stress-related brain emotional systems. Since the discovery by Wylie Vale and his colleagues of Corticotropin-Releasing Factor (CRF) and the structurally-related urocortins, CRF systems have emerged as mediators of the body’s response to stress. Relatedly, CRF systems have a prominent role in driving addiction via actions in the central extended amygdala, producing anxiety-like behavior, reward deficits, excessive, compulsive-like drug self-administration and stress-induced reinstatement of drug seeking. CRF neuron activation in the medial prefrontal cortex may also contribute to the loss of control. Polymorphisms in CRF system molecules are associated with drug use phenotypes in humans, often in interaction with stress history. Drug discovery efforts have yielded brain-penetrant CRF 1 antagonists with activity in preclinical models of addiction. The results support the hypothesis that brain CRF–CRF 1 systems contribute to the etiology and maintenance of addiction.
-
allostasis and addiction role of the dopamine and corticotropin releasing Factor systems
Physiology & Behavior, 2012Co-Authors: Olivier George, Michel Le Moal, George F. KoobAbstract:Allostasis, originally conceptualized to explain persistent morbidity of arousal and autonomic function, is defined as the process of achieving stability through physiological or behavioral change. Two types of biological processes have been proposed to describe the mechanisms underlying allostasis in drug addiction, a within-system adaptation and a between-system adaptation. In the within-system process, the drug elicits an opposing, neutralizing reaction within the same system in which the drug elicits its primary and unconditioned reinforcing actions, while in the between-system process, different neurobiological systems that the one initially activated by the drug are recruited. In this review, we will focus our interest on alterations in the dopaminergic and corticotropin releasing Factor systems as within-system and between-system neuroadaptations respectively, that underlie the opponent process to drugs of abuse. We hypothesize that repeated compromised activity in the dopaminergic system and sustained activation of the CRF-CRF1R system with withdrawal episodes may lead to an allostatic load contributing significantly to the transition to drug addiction.
-
progress in corticotropin releasing Factor 1 antagonist development
Drug Discovery Today, 2010Co-Authors: Eric P. Zorrilla, George F. KoobAbstract:Corticotropin releasing Factor (CRF) receptor antagonists have been sought since the stress-secreted peptide was isolated in 1981. Although evidence is mixed concerning the efficacy of CRF 1 antagonists as antidepressants, CRF 1 antagonists might be novel pharmacotherapies for anxiety and addiction. Progress in understanding the two-domain model of ligand–receptor interactions for CRF family receptors might yield chemically novel CRF 1 receptor antagonists, including peptide CRF 1 antagonists, antagonists with signal transduction selectivity and nonpeptide CRF 1 antagonists that act via the extracellular (rather than transmembrane) domains. Novel ligands that conform to the prevalent pharmacophore and exhibit drug-like pharmacokinetic properties have been identified. The therapeutic utility of CRF 1 antagonists should soon be clearer: several small molecules are currently in Phase II/III clinical trials for depression, anxiety and irritable bowel syndrome.
-
neurobiological mechanisms of addiction focus on corticotropin releasing Factor
Current opinion in investigational drugs, 2010Co-Authors: George F. Koob, Eric P. ZorrillaAbstract:Drug addiction is a chronically relapsing disorder that is characterized by a compulsion to take drugs and loss of control in limiting intake. Medications that are on the market for the treatment of drug addiction target either the direct reinforcing effects of abuse (eg, naltrexone) or the consequent protracted abstinence syndrome (eg, acamprosate). Both conceptual and neurobiological advances in research have suggested that brain stress systems contribute to the withdrawal/negative affect and preoccupation/anticipation stages of the addiction cycle that promote the compulsivity of drug-taking in addiction. Validated animal models of the stress component of addiction and improved understanding of the neurocircuitry and neuropharmacological mechanisms involved in perturbations of this component suggest that Corticotropin-Releasing Factor systems are a viable target for the development of future medications for drug addiction.
-
a key role for corticotropin releasing Factor in alcohol dependence
Trends in Neurosciences, 2007Co-Authors: Markus Heilig, George F. KoobAbstract:Recent data indicate that alcohol dependence induces long-term neuroadaptations that recruit a negative emotional state. This leads to excessive alcohol ingestion motivated by relief of negative emotionality. A key mechanism in this transition to negative reinforcement is a recruitment of Corticotropin-Releasing Factor (CRF) signaling within the amygdala. Long term upregulation of CRF 1 receptors is observed in the amygdala following a history of dependence, and CRF antagonists selectively block emotionality, excessive alcohol drinking and stress-induced reinstatement of alcohol-seeking in post-dependent animals. Innate upregulation of CRF 1 receptor expression mimics the post-dependent phenotype, both with regard to emotional responses and ethanol self-administration. Therefore, the CRF system is emerging as a key element of the neuroadaptive changes driving alcoholism and as a major target for its treatment.
Rita J. Valentino - One of the best experts on this subject based on the ideXlab platform.
-
increased vulnerability of the brain norepinephrine system of females to corticotropin releasing Factor overexpression
Molecular Psychiatry, 2013Co-Authors: Debra A Bangasser, E.j. Van Bockstaele, B A S Reyes, David A Piel, V Garachh, Xy Zhang, Zach Plona, Sheryl G Beck, Rita J. ValentinoAbstract:Increased vulnerability of the brain norepinephrine system of females to Corticotropin-Releasing Factor overexpression
-
The Bladder-Brain Connection: Putative Role of Corticotropin-Releasing Factor
Nature reviews. Urology, 2010Co-Authors: Rita J. Valentino, Susan K. Wood, Alan J. Wein, Stephen A. ZdericAbstract:The coordination of pelvic visceral activity with appropriate elimination behaviors is a complex task that requires reciprocal communication between the brain and pelvic organs. Barrington's nucleus, located in the pons, is central to a circuit involved in this function. Barrington's nucleus neurons project to both pelvic visceral motorneurons and cerebral norepinephrine neurons that modulate behavior. This circuit coordinates the descending limb of the micturition reflex with a central limb that initiates arousal and shifts the focus of attention to facilitate elimination behavior. The same circuitry that links the bladder and brain enables pathological processes in one target of the circuit to be expressed in the other. Urological disorders can, therefore, have cognitive and behavioral consequences by affecting components of this circuit; and in the opposing direction, psychosocial stressors can produce voiding dysfunctions and bladder pathology. The stress-related neuropeptide, Corticotropin-Releasing Factor, which is prominent in Barrington's nucleus neurons, is a potential mediator of these effects.
-
sex differences in corticotropin releasing Factor receptor signaling and trafficking potential role in female vulnerability to stress related psychopathology
Molecular Psychiatry, 2010Co-Authors: Debra A Bangasser, Andre L. Curtis, E.j. Van Bockstaele, Beverly A S Reyes, Thelma Bethea, Ioannis Parastatidis, Harry Ischiropoulos, Rita J. ValentinoAbstract:Sex differences in Corticotropin-Releasing Factor receptor signaling and trafficking: potential role in female vulnerability to stress-related psychopathology
-
evidence for corticotropin releasing Factor regulation of serotonin in the lateral septum during acute swim stress adaptation produced by repeated swimming
Psychopharmacology, 2002Co-Authors: Michelle L Price, Rita J. Valentino, Lynn G Kirby, Irwin LuckiAbstract:Rationale. Swim stress decreases extracellular serotonin (5-HT) levels in the rat lateral septum, and adaptation to this effect occurs with repeated swimming. Corticotropin-Releasing Factor (CRF) administered into the dorsal raphe nucleus (DRN) also decreases 5-HT release in the lateral septum, suggesting that CRF may mediate the effects of swim stress.
-
Corticotropin-Releasing Factor: Putative Neurotransmitter Actions of a Neurohormone
Hormones Brain and Behavior, 2002Co-Authors: Rita J. Valentino, Elisabeth J. Van BockstaeleAbstract:Publisher Summary This chapter discusses the Corticotropin-Releasing Factor (CRF). CRF was originally characterized as the hypothalamic neurohormone that promotes adrenocorticotropin release in response to stressors, initiating the cascade of responses linked to corticosteroid secretion. This endocrine limb of the stress response is generally considered a hallmark of stress. However, the stress response is also characterized by autonomic, behavioral, and immunological changes as a consequence of the engagement of specific neuronal systems. Following the identification and characterization of CRF as a neurohormone, convergent findings from several laboratories implicated CRF as a neuromodulator that was involved in engaging these neuronal systems during stress. It is important to note that the central administration of CRF antibody or antagonists could prevent similar autonomic and behavioral stress-elicited effects, emphasizing a role for central CRF in these nonendocrine aspects of stress.
Felice Petraglia - One of the best experts on this subject based on the ideXlab platform.
-
activin a corticotropin releasing Factor and prostaglandin f2α increase immunoreactive oxytocin release from cultured human placental cells
Placenta, 1996Co-Authors: Pasquale Florio, Steve Sutton, M Lombardo, R Gallo, C Di Carlo, Ar Genazzani, Felice PetragliaAbstract:Abstract The aim of the present study was to investigate the presence of the immunoreactive oxytocin in human placental extracts and putative Factors regulating the release of immunoreactive oxytocin from cultured human placental cells. Fresh placental tissue was collected from pregnant women at term and dissected of membranes (n=5). Presence of immunoreactive oxytocin in trophoblast tissue was evaluated by a specific radio-immunoassay after acidic extraction and high-pressure liquid chromatography. In a second set of experiments, primary cultures of placental cells were performed and, 48–72 h after dissociation, the effect of arginine vasopressin, Corticotropin-Releasing Factor, neuropeptide Y, activin A, inhibin A, noradrenaline or prostaglandins on immunoreactive oxytocin level in culture medium was investigated. The presence of immunoreactive oxytocin was shown in the acidic extract of trophoblast at term, and in the culture medium of human placental cells, and it was identical to the native peptide. The addition of Corticotropin-Releasing Factor or arginine vasopressin, but not of neuropeptide Y, increased the, release of immunoreactive oxytocin three- to fourfold from placental cells, with a dose-dependent effect (P
Gina L. Forster - One of the best experts on this subject based on the ideXlab platform.
-
Chronic amphetamine treatment enhances Corticotropin-Releasing Factor-induced serotonin release in the amygdala.
European Journal of Pharmacology, 2010Co-Authors: Jamie L. Scholl, Shawn M Vuong, Gina L. ForsterAbstract:Abstract Amphetamine use is associated with dysphoric states, including heightened anxiety, that emerge within 24 h of withdrawal from the drug. Corticotropin-Releasing Factor increases serotonin release in the central nucleus of the amygdala, and this neurochemical circuitry may play a role in mediating fear and anxiety states. We have previously shown that chronic amphetamine treatment increases Corticotropin-Releasing Factor receptor type-2 levels in the serotonergic dorsal raphe nucleus of the rat. Therefore, we hypothesized that chronic amphetamine treatment would enhance the amygdalar serotonergic response to Corticotropin-Releasing Factor infused into the dorsal raphe nucleus. Male rats were injected once-daily with d-amphetamine (2.5 mg/kg i.p., or saline) for two weeks. Serotonin release within the central nucleus of the amygdala in response to intra-raphe infusion of Corticotropin-Releasing Factor (100 ng) was measured 24 h after the last treatment in urethane-anesthetized (1.8 mg/kg, i.p.) rats using in vivo microdialysis. Rats pretreated with amphetamine showed significantly enhanced serotonin release in the central nucleus of the amygdala in response to Corticotropin-Releasing Factor infusion when compared to saline pretreated rats. Furthermore, this enhanced response was blocked by the Corticotropin-Releasing Factor type-2 receptor antagonist antisauvagine-30 (2 μg) infused into the dorsal raphe nucleus. These results suggest increased sensitivity to Corticotropin-Releasing Factor as mediated by type-2 receptors following chronic amphetamine treatment, which may underlie dysphoric states observed during amphetamine withdrawal.
-
Restraint stress increases serotonin release in the central nucleus of the amygdala via activation of Corticotropin-Releasing Factor receptors.
Brain research bulletin, 2008Co-Authors: Na Feng, Kenneth J. Renner, Gina L. ForsterAbstract:Abstract Decreases in serotonergic activity in the central nucleus of the amygdala reduce responses to stressors, suggesting an important role for serotonin in this region of the amygdala in stress reactivity. However, it is not known whether exposure to stressors actually increases serotonin release in the central nucleus of the amygdala. The current experiment tested the hypothesis that restraint stress increases extracellular serotonin within the central nucleus of the amygdala and adjacent medial amygdala using in vivo microdialysis in awake male rats during the dark phase of the light–dark cycle. Serotonin release in the central nucleus increased immediately in response to restraint stress. In contrast, there was no change in serotonin release within the adjacent medial amygdala during or following restraint. Since Corticotropin-Releasing Factor is an important mediator of both responses to stressors and serotonergic activity, subsequent experiments tested the hypothesis that central nucleus serotonergic response to restraint stress is mediated by central Corticotropin-Releasing Factor receptors. Administration of the Corticotropin-Releasing Factor type 1 and 2 receptor antagonist d -Phe-CRF (icv, 10 μg/5 μl) prior to restraint stress suppressed restraint-induced serotonin release in the central nucleus. The results suggest that restraint stress rapidly and selectively increases serotonin release in the central nucleus of the amygdala by the activation of central Corticotropin-Releasing Factor receptors. Furthermore, the results imply that Corticotropin-Releasing Factor mediated serotonergic activity in central nucleus of the amygdala may be an important component of a stress response.
T Sherrin - One of the best experts on this subject based on the ideXlab platform.
-
chronic stimulation of corticotropin releasing Factor receptor 1 enhances the anxiogenic response of the cholecystokinin system
Molecular Psychiatry, 2009Co-Authors: T Sherrin, Cedomir Todorovic, T Zeyda, Chay Hoon Tan, Peiyan Wong, Yz ZhuAbstract:Chronic stimulation of Corticotropin-Releasing Factor receptor 1 enhances the anxiogenic response of the cholecystokinin system
