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Article ; Online: Effect of TAAR1/5-HT

Hopkins, Seth C / Dedic, Nina / Koblan, Kenneth S

2021 Volume 11, Issue 1, Page(s) 228

Abstract: SEP-363856 is a trace amine-associated receptor 1 (TAAR1) and 5-hydroxytryptamine type 1A (5- ... ...

Abstract	SEP-363856 is a trace amine-associated receptor 1 (TAAR1) and 5-hydroxytryptamine type 1A (5-HT
MeSH term(s)	Cross-Over Studies ; Double-Blind Method ; Humans ; Male ; Pyrans ; Receptors, G-Protein-Coupled ; Serotonin ; Sleep ; Sleep, REM
Chemical Substances	Pyrans ; Receptors, G-Protein-Coupled ; SEP-363856 ; Serotonin (333DO1RDJY) ; Trace amine-associated receptor 1 (XMC8VP6RI2)
Language	English
Publishing date	2021-04-20
Publishing country	United States
Document type	Journal Article ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
ZDB-ID	2609311-X
ISSN	2158-3188 ; 2158-3188
ISSN (online)	2158-3188
ISSN	2158-3188
DOI	10.1038/s41398-021-01331-9
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Article ; Online: TAAR1 agonist ulotaront delays gastric emptying of solids in patients with schizophrenia and concurrent metabolic syndrome with prediabetes.

Milanović, Snežana / Dedic, Nina / Lew, Robert / Burton, Duane / Koblan, Kenneth S / Camilleri, Michael / Hopkins, Seth C

Diabetes, obesity & metabolism

2024

Abstract: Background: Metabolic syndrome (MetS), which can be induced or exacerbated by the current class of antipsychotic drugs, is highly prevalent in patients with schizophrenia and presents significant challenges to lifetime disease management. Supported by ... ...

Abstract	Background: Metabolic syndrome (MetS), which can be induced or exacerbated by the current class of antipsychotic drugs, is highly prevalent in patients with schizophrenia and presents significant challenges to lifetime disease management. Supported by initial clinical results, trace amine-associated receptor 1 (TAAR1) agonists have emerged as potential novel treatments for schizophrenia. Notably, non-clinical studies have also shown weight-lowering and glucoregulatory effects of TAAR1 agonists, including the investigational agent ulotaront. However, the translatability of these findings to humans has not been adequately assessed. Given that delayed gastric emptying (GE) was identified as a potential mechanism contributing to the metabolic benefits of TAAR1 agonists in rodents, the aim of this study was to evaluate the effect of ulotaront on GE in patients with schizophrenia and concurrent MetS with prediabetes. Methods: Patients with schizophrenia were randomized to receive a single oral dose of ulotaront (150 mg) and their previous antipsychotic (PA) in an open-label, crossover, two-sequence design (NCT05402111). Eligible participants fulfilled at least three of five MetS criteria and had prediabetes defined by elevated glycated haemoglobin (5.7-6.4%) and/or fasting homeostatic model assessment of insulin resistance (i.e. ≥2.22). Following an overnight fast and 4 h post-dose, participants ingested a Results: Thirty-one adults were randomized and 27 completed the study. Ulotaront significantly delayed GE of solids [median GE T Conclusion: Ulotaront delayed the GE of solids in patients with schizophrenia and concurrent MetS with prediabetes. Additional studies are needed to assess whether treatment with TAAR1 agonists is associated with weight loss and glucoregulatory improvement.
Language	English
Publishing date	2024-03-27
Publishing country	England
Document type	Journal Article
ZDB-ID	1454944-x
ISSN	1463-1326 ; 1462-8902
ISSN (online)	1463-1326
ISSN	1462-8902
DOI	10.1111/dom.15569
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Article ; Online: Ulotaront: review of preliminary evidence for the efficacy and safety of a TAAR1 agonist in schizophrenia.

Achtyes, Eric D / Hopkins, Seth C / Dedic, Nina / Dworak, Heather / Zeni, Courtney / Koblan, Kenneth

European archives of psychiatry and clinical neuroscience

2023 Volume 273, Issue 7, Page(s) 1543–1556

Abstract: Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 clinical development for the treatment of schizophrenia. Ulotaront was discovered through a unique, target-agnostic approach optimized to identify drug candidates lacking D2 and ... ...

Abstract	Ulotaront is a trace amine-associated receptor 1 (TAAR1) agonist in Phase 3 clinical development for the treatment of schizophrenia. Ulotaront was discovered through a unique, target-agnostic approach optimized to identify drug candidates lacking D2 and 5-HT2A receptor antagonism, while demonstrating an antipsychotic-like phenotypic profile in vivo. The mechanism of action (MOA) of ulotaront is thought to be mediated by agonism at TAAR1 and serotonin 5-HT1A receptors. Ulotaront has completed two Phase 2 trials (4-week acute study and 26-week open-label extension) which led to Breakthrough Therapy Designation from the US Food and Drug Administration for the treatment of schizophrenia. In the double-blind, placebo-controlled, acute study, ulotaront was associated with significant (p < 0.001) improvement in Positive and Negative Syndrome Scale (PANSS) total score (effect size [ES]: 0.45), with improvements vs. placebo also observed across secondary endpoints. Post-hoc analyses of the acute trial revealed additional evidence to support the effect of ulotaront on negative symptoms. In the 4-week study, ulotaront was well-tolerated, with an incidence of adverse events (AEs) numerically lower compared to placebo (45.8% vs. 50.4%; with a number needed to harm [NNH] for individual ulotaront AEs all > 40). The open-label extension demonstrated further improvement across schizophrenia symptoms and confirmed the tolerability of ulotaront, with a 6-month completion rate of 67%. Based on current data, ulotaront shows potential to be a first-in-class TAAR1 agonist for the treatment of schizophrenia with a safety and efficacy profile distinct from current antipsychotics.
MeSH term(s)	United States ; Humans ; Schizophrenia/diagnosis ; Treatment Outcome ; Antipsychotic Agents/adverse effects ; Randomized Controlled Trials as Topic
Chemical Substances	Trace amine-associated receptor 1 (XMC8VP6RI2) ; SEP-363856 ; Antipsychotic Agents
Language	English
Publishing date	2023-05-10
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	1045583-8
ISSN	1433-8491 ; 0175-758X ; 0940-1334
ISSN (online)	1433-8491
ISSN	0175-758X ; 0940-1334
DOI	10.1007/s00406-023-01580-3
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Article ; Online: Genetic Algorithms as Tool for Development of Balanced Curriculum

Fuad Dedić / Nina Bijedić / Dražena Gašpar

Interdisciplinary Description of Complex Systems, Vol 18, Iss 2-B, Pp 175-

2020 Volume 193

Abstract: The article presents research about the use of genetic algorithms in the analysis of the interrelation among curriculum courses in higher education. The authors used genetic algorithms as a method to analyse the influence that achieved grades in ... ...

Abstract	The article presents research about the use of genetic algorithms in the analysis of the interrelation among curriculum courses in higher education. The authors used genetic algorithms as a method to analyse the influence that achieved grades in predictors’ courses have on achieved grades in dependent courses as well as to observe whether the genetic algorithms can contribute to improving the curriculum. The research was based on a set of data related to the success of students from the Faculty of Information Technologies at the University ‘Džemal Bijedić’ in Mostar, Bosnia and Herzegovina. The aim was to anticipate students’ grades based on the grades they obtained in previous semester’s courses. This research should help educational institutions to evaluate the suitability of the sequence of courses within the curriculum in order to enable personalized learning paths, make the teaching processes more efficient, and promote a balanced curriculum. Namely, a good curriculum can attract new students, improve the success rate of enrolled students, and increase the quality and visibility of the institution. Since the genetic algorithm is search techniques for handling complex spaces, we can use it for the research at each stage of the educational process. Analyses of quantitative data using a genetic algorithm can help educational institutions improve the quality of teaching.
Keywords	balanced curriculum ; curriculum evaluation ; genetic algorithm ; personalized learning ; Social sciences (General) ; H1-99
Subject code	370
Language	English
Publishing date	2020-07-01T00:00:00Z
Publisher	Croatian Interdisciplinary Society
Document type	Article ; Online
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Article ; Online: In Vitro ADME and Preclinical Pharmacokinetics of Ulotaront, a TAAR1/5-HT

Xiao, Guangqing / Chen, Yu-Luan / Dedic, Nina / Xie, Linghong / Koblan, Kenneth S / Galluppi, Gerald R

Pharmaceutical research

2022 Volume 39, Issue 5, Page(s) 837–850

Abstract: Purpose: Ulotaront (SEP-363856) is a TAAR1 agonist with 5-HT: Methods: Solubility, permeability, plasma protein binding, CYP inhibition and induction, transporter inhibition and uptake studies were conducted in vitro. Phenotyping studies were ... ...

Abstract	Purpose: Ulotaront (SEP-363856) is a TAAR1 agonist with 5-HT Methods: Solubility, permeability, plasma protein binding, CYP inhibition and induction, transporter inhibition and uptake studies were conducted in vitro. Phenotyping studies were conducted using recombinant human CYPs and FMOs, human liver microsomes and human liver homogenates. Preclinical plasma and brain pharmacokinetics were determined after a single intraperitoneal, intravenous, and oral administration of ulotaront. Results: Ulotaront is a compound of high solubility, high permeability, and low binding to plasma proteins. Ulotaront metabolism is mediated via both NADPH-dependent and NADPH-independent pathways, with CYP2D6 as the major metabolizing enzyme. Ulotaront is an inducer of CYP2B6, and an inhibitor of CYP2D6, OCT1 and OCT2, while SEP-383103 is neither a CYP inducer nor a potent inhibitor of CYPs and human transporters. Ulotaront exhibits rapid absorption, greater than 70% bioavailability, approximately 3.5 L/kg volume of distribution, 1.5-4 h half-life, 12-43 ml/min/kg clearance, and good penetration across the blood-brain barrier in preclinical species. Conclusions: Ulotaront has been designated as a BCS1 compound by US FDA. The ability of ulotaront to penetrate the blood-brain barrier for CNS targeting has been demonstrated in mice and rats. The potential for ulotaront and SEP-383103 to act as perpetrators of CYP and transporter-mediated DDIs is predicted to be remote.
MeSH term(s)	Animals ; Cytochrome P-450 CYP2D6/metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Mice ; Microsomes, Liver/metabolism ; NADP/metabolism ; NADP/pharmacology ; Pharmaceutical Preparations/metabolism ; Rats ; Receptor, Serotonin, 5-HT1A/metabolism ; Schizophrenia/drug therapy
Chemical Substances	Pharmaceutical Preparations ; Receptor, Serotonin, 5-HT1A (112692-38-3) ; NADP (53-59-8) ; Cytochrome P-450 Enzyme System (9035-51-2) ; Cytochrome P-450 CYP2D6 (EC 1.14.14.1)
Language	English
Publishing date	2022-04-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	843063-9
ISSN	1573-904X ; 0724-8741 ; 0739-0742
ISSN (online)	1573-904X
ISSN	0724-8741 ; 0739-0742
DOI	10.1007/s11095-022-03267-1
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Article ; Online: Therapeutic Potential of TAAR1 Agonists in Schizophrenia: Evidence from Preclinical Models and Clinical Studies.

Dedic, Nina / Dworak, Heather / Zeni, Courtney / Rutigliano, Grazia / Howes, Oliver D

International journal of molecular sciences

2021 Volume 22, Issue 24

Abstract: Trace amine-associated receptor 1 (TAAR1) has emerged as a promising therapeutic target for neuropsychiatric disorders due to its ability to modulate monoaminergic and glutamatergic neurotransmission. In particular, agonist compounds have generated ... ...

Abstract	Trace amine-associated receptor 1 (TAAR1) has emerged as a promising therapeutic target for neuropsychiatric disorders due to its ability to modulate monoaminergic and glutamatergic neurotransmission. In particular, agonist compounds have generated interest as potential treatments for schizophrenia and other psychoses due to TAAR1-mediated regulation of dopaminergic tone. Here, we review unmet needs in schizophrenia, the current state of knowledge in TAAR1 circuit biology and neuropharmacology, including preclinical behavioral, imaging, and cellular evidence in glutamatergic, dopaminergic and genetic models linked to the pathophysiology of psychotic, negative and cognitive symptoms. Clinical trial data for TAAR1 drug candidates are reviewed and contrasted with antipsychotics. The identification of endogenous TAAR1 ligands and subsequent development of small-molecule agonists has revealed antipsychotic-, anxiolytic-, and antidepressant-like properties, as well as pro-cognitive and REM-sleep suppressing effects of TAAR1 activation in rodents and non-human primates. Ulotaront, the first TAAR1 agonist to progress to randomized controlled clinical trials, has demonstrated efficacy in the treatment of schizophrenia, while another, ralmitaront, is currently being evaluated in clinical trials in schizophrenia. Coupled with the preclinical findings, this provides a rationale for further investigation and development of this new pharmacological class for the treatment of schizophrenia and other psychiatric disorders.
MeSH term(s)	Animals ; Antipsychotic Agents/pharmacology ; Antipsychotic Agents/therapeutic use ; Clinical Trials as Topic ; Disease Models, Animal ; Dopamine/metabolism ; Glutamic Acid/metabolism ; Humans ; Receptors, G-Protein-Coupled/agonists ; Receptors, G-Protein-Coupled/metabolism ; Schizophrenia/drug therapy ; Schizophrenia/metabolism ; Small Molecule Libraries/pharmacology ; Small Molecule Libraries/therapeutic use
Chemical Substances	Antipsychotic Agents ; Receptors, G-Protein-Coupled ; Small Molecule Libraries ; Glutamic Acid (3KX376GY7L) ; Dopamine (VTD58H1Z2X) ; Trace amine-associated receptor 1 (XMC8VP6RI2)
Language	English
Publishing date	2021-12-07
Publishing country	Switzerland
Document type	Comparative Study ; Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms222413185
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Article ; Online: TAAR1 agonists improve glycemic control, reduce body weight and modulate neurocircuits governing energy balance and feeding.

Dedic, Nina / Wang, Lien / Hajos-Korcsok, Eva / Hecksher-Sørensen, Jacob / Roostalu, Urmas / Vickers, Steven P / Wu, Serena / Anacker, Christoph / Synan, Colleen / Jones, Philip G / Milanovic, Snezana / Hopkins, Seth C / Bristow, Linda J / Koblan, Kenneth S

Molecular metabolism

2024 Volume 80, Page(s) 101883

Abstract: Objective: Metabolic Syndrome, which can be induced or exacerbated by current antipsychotic drugs (APDs), is highly prevalent in schizophrenia patients. Recent preclinical and clinical evidence suggest that agonists at trace amine-associated receptor 1 ( ...

Abstract	Objective: Metabolic Syndrome, which can be induced or exacerbated by current antipsychotic drugs (APDs), is highly prevalent in schizophrenia patients. Recent preclinical and clinical evidence suggest that agonists at trace amine-associated receptor 1 (TAAR1) have potential as a new treatment option for schizophrenia. Intriguingly, preclinical tudies have also identified TAAR1 as a novel regulator of metabolic control. Here we evaluated the effects of three TAAR1 agonists, including the clinical development candidate ulotaront, on body weight, metabolic parameters and modulation of neurocircuits implicated in homeostatic and hedonic feeding. Methods: Effects of TAAR1 agonists (ulotaront, RO5166017 and/or RO5263397) on body weight, food intake and/or metabolic parameters were investigated in rats fed a high-fat diet (HFD) and in a mouse model of diet-induced obesity (DIO). Body weight effects were also determined in a rat and mouse model of olanzapine-, and corticosterone-induced body weight gain, respectively. Glucose tolerance was assessed in lean and diabetic db/db mice and fasting plasma glucose and insulin examined in DIO mice. Effects on gastric emptying were evaluated in lean mice and rats. Drug-induced neurocircuit modulation was evaluated in mice using whole-brain imaging of c-fos protein expression. Results: TAAR1 agonists improved oral glucose tolerance by inhibiting gastric emptying. Sub-chronic administration of ulotaront in rats fed a HFD produced a dose-dependent reduction in body weight, food intake and liver triglycerides compared to vehicle controls. In addition, a more rapid reversal of olanzapine-induced weight gain and food intake was observed in HFD rats switched to ulotaront or RO5263397 treatment compared to those switched to vehicle. Chronic ulotaront administration also reduced body weight and improved glycemic control in DIO mice, and normalized corticosterone-induced body weight gain in mice. TAAR1 activation increased neuronal activity in discrete homeostatic and hedonic feeding centers located in the dorsal vagal complex and hypothalamus with concurrent activation of several limbic structures. Conclusion: The current data demonstrate that TAAR1 agonists, as a class, not only lack APD-induced metabolic liabilities but can reduce body weight and improve glycemic control in rodent models. The underlying mechanisms likely include TAAR1-mediated peripheral effects on glucose homeostasis and gastric emptying as well as central regulation of energy balance and food intake.
MeSH term(s)	Humans ; Rats ; Mice ; Animals ; Olanzapine ; Glycemic Control ; Corticosterone ; Body Weight ; Weight Gain ; Disease Models, Animal ; Glucose ; Receptors, G-Protein-Coupled
Chemical Substances	Trace amine-associated receptor 1 (XMC8VP6RI2) ; Olanzapine (N7U69T4SZR) ; Corticosterone (W980KJ009P) ; Glucose (IY9XDZ35W2) ; Receptors, G-Protein-Coupled
Language	English
Publishing date	2024-01-16
Publishing country	Germany
Document type	Journal Article
ZDB-ID	2708735-9
ISSN	2212-8778 ; 2212-8778
ISSN (online)	2212-8778
ISSN	2212-8778
DOI	10.1016/j.molmet.2024.101883
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Article ; Online: TAAR1 agonist ulotaront modulates striatal and hippocampal glutamate function in a state-dependent manner.

Yang, Sung M / Ghoshal, Ayan / Hubbard, Jeffrey M / Gackière, Florian / Teyssié, Romain / Neale, Stuart A / Hopkins, Seth C / Koblan, Kenneth S / Bristow, Linda J / Dedic, Nina

Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology

2023

Abstract: Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated ... ...

Abstract	Aberrant dopaminergic and glutamatergic function, particularly within the striatum and hippocampus, has repeatedly been associated with the pathophysiology of schizophrenia. Supported by preclinical and recent clinical data, trace amine-associated receptor 1 (TAAR1) agonism has emerged as a potential new treatment approach for schizophrenia. While current evidence implicates TAAR1-mediated regulation of dopaminergic tone as the primary circuit mechanism, little is known about the effects of TAAR1 agonists on the glutamatergic system and excitation-inhibition balance. Here we assessed the impact of ulotaront (SEP-363856), a TAAR1 agonist in Phase III clinical development for schizophrenia, on glutamate function in the mouse striatum and hippocampus. Ulotaront reduced spontaneous glutamatergic synaptic transmission and neuronal firing in striatal and hippocampal brain slices, respectively. Interestingly, ulotaront potentiated electrically-evoked excitatory synaptic transmission in both brain regions, suggesting the ability to modulate glutamatergic signaling in a state-dependent manner. Similar striatal effects were also observed with the TAAR1 agonist, RO5166017. Furthermore, we show that ulotaront regulates excitation-inhibition balance in the striatum by specifically modulating glutamatergic, but not GABAergic, spontaneous synaptic events. These findings expand the mechanistic circuit hypothesis of ulotaront and TAAR1 agonists, which may be uniquely positioned to normalize both the excessive dopaminergic tone and regulate abnormal glutamatergic function associated with schizophrenia.
Language	English
Publishing date	2023-12-19
Publishing country	England
Document type	Journal Article
ZDB-ID	639471-1
ISSN	1740-634X ; 0893-133X
ISSN (online)	1740-634X
ISSN	0893-133X
DOI	10.1038/s41386-023-01779-x
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Article: Determinants of job satisfaction of healthcare professionals in public hospitals in Belgrade, Serbia--Cross-sectional analysis.

Kuburović, Nina B / Dedić, Velimir / Djuricić, Slavisa / Kuburović, Vladimir

Srpski arhiv za celokupno lekarstvo

2016 Volume 144, Issue 3-4, Page(s) 165–173

Abstract: Introduction: The quality of health care significantly depends on the satisfaction of the employees.: Objective: The objective of this study was to establish the level of professional satisfaction of healthcare professionals in state hospitals in ... ...

Abstract	Introduction: The quality of health care significantly depends on the satisfaction of the employees. Objective: The objective of this study was to establish the level of professional satisfaction of healthcare professionals in state hospitals in Belgrade, Serbia, and to determine and to rank the factors which impact on their satisfaction or dissatisfaction. Method: Professional satisfaction survey was designed and conducted as a cross-sectional study in 2008. Completed questionnaires were returned by 6,595 healthcare professionals from Belgrade's hospitals. Statistical analysis was performed using the Student's t-test, χ² test and ANOVA. Factor analysis was applied in order to define determinants of professional satisfaction, i.e. dissatisfaction. Results: This study showed that the degree of professional satisfaction of Serbian healthcare professionals was low. The main causes of professionals'dissatisfaction were wages, equipment, the possibility of continuous medical education/training and the opportunities for professional development. Healthcare professionals with university education were more satisfied with all the individual aspects of job satisfaction than those with secondary school and college education. Conclusion: There were significantly more healthcare professionals satisfied with their job among males, older than 60 years, in the age group 50-59 years, with managerial function, and with 30 or more years of service. Development strategy of human resources in the Serbian health care system would significantly improve the professional satisfaction and quality of the provided health care.
MeSH term(s)	Adult ; Age Factors ; Aged ; Allied Health Personnel ; Career Mobility ; Cross-Sectional Studies ; Delivery of Health Care ; Education, Continuing ; Equipment and Supplies, Hospital ; Female ; Health Personnel ; Hospitals, Public ; Humans ; Job Satisfaction ; Male ; Middle Aged ; Nurses ; Pharmacists ; Physicians ; Salaries and Fringe Benefits ; Serbia ; Sex Factors ; Surveys and Questionnaires ; Young Adult
Language	English
Publishing date	2016-03
Publishing country	Serbia
Document type	Journal Article
ZDB-ID	128567-1
ISSN	0370-8179 ; 0354-2793 ; 0049-0210
ISSN	0370-8179 ; 0354-2793 ; 0049-0210
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Article ; Online: The CRF Family of Neuropeptides and their Receptors - Mediators of the Central Stress Response.

Dedic, Nina / Chen, Alon / Deussing, Jan M

Current molecular pharmacology

2017 Volume 11, Issue 1, Page(s) 4–31

Abstract: Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic- ... ...

Abstract	Background: Dysregulated stress neurocircuits, caused by genetic and/or environmental changes, underlie the development of many neuropsychiatric disorders. Corticotropin-releasing factor (CRF) is the major physiological activator of the hypothalamic-pituitary-adrenal (HPA) axis and consequently a primary regulator of the mammalian stress response. Together with its three family members, urocortins (UCNs) 1, 2, and 3, CRF integrates the neuroendocrine, autonomic, metabolic and behavioral responses to stress by activating its cognate receptors CRFR1 and CRFR2. Objective: Here we review the past and current state of the CRF/CRFR field, ranging from pharmacological studies to genetic mouse models and virus-mediated manipulations. Results: Although it is well established that CRF/CRFR1 signaling mediates aversive responses, including anxiety and depression-like behaviors, a number of recent studies have challenged this viewpoint by revealing anxiolytic and appetitive properties of specific CRF/CRFR1 circuits. In contrast, the UCN/CRFR2 system is less well understood and may possibly also exert divergent functions on physiology and behavior depending on the brain region, underlying circuit, and/or experienced stress conditions. Conclusion: A plethora of available genetic tools, including conventional and conditional mouse mutants targeting CRF system components, has greatly advanced our understanding about the endogenous mechanisms underlying HPA system regulation and CRF/UCN-related neuronal circuits involved in stress-related behaviors. Yet, the detailed pathways and molecular mechanisms by which the CRF/UCN-system translates negative or positive stimuli into the final, integrated biological response are not completely understood. The utilization of future complementary methodologies, such as cell-type specific Cre-driver lines, viral and optogenetic tools will help to further dissect the function of genetically defined CRF/UCN neurocircuits in the context of adaptive and maladaptive stress responses.
MeSH term(s)	Animals ; Corticotropin-Releasing Hormone/metabolism ; Genetic Engineering ; Humans ; Receptors, Corticotropin-Releasing Hormone/metabolism ; Signal Transduction ; Stress, Physiological ; Viruses/metabolism
Chemical Substances	Receptors, Corticotropin-Releasing Hormone ; Corticotropin-Releasing Hormone (9015-71-8)
Language	English
Publishing date	2017-03-08
Publishing country	United Arab Emirates
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ISSN	1874-4702
ISSN (online)	1874-4702
DOI	10.2174/1874467210666170302104053
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