The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Gitte M Knudsen - One of the best experts on this subject based on the ideXlab platform.
-
men with high Serotonin 1B Receptor binding respond to provocations with heightened amygdala reactivity
NeuroImage, 2018Co-Authors: Sofi Da Cunhabang, Liv V Hjordt, Patrick M Fisher, Erik Perfalk, Vincent Beliveau, Klaus K Holst, Gitte M KnudsenAbstract:Abstract Serotonin signalling influences amygdala reactivity to threat-related emotional facial expressions in healthy adults, but in vivo Serotonin signalling has never been investigated in the context of provocative stimuli in aggressive individuals. The aim of this study was to evaluate associations between Serotonin 1B Receptor (5-HT 1B R) levels and brain reactivity to provocations. We quantified regional 5-HT 1B R binding using [ 11 C]AZ10419369 positron emission tomography (PET) and measured brain activation following provocations with functional magnetic resonance imaging (fMRI) in eighteen violent offenders and 25 healthy control subjects. The point-subtraction aggression paradigm (PSAP) was used in fMRI to elicit provocations in terms of monetary subtractions from a fictive opponent. We estimated global 5-HT 1B R binding using a linear structural equation model, with a single latent response variable (LV 1B ) modelling shared correlation between 5-HT 1B R binding across multiple brain regions (neocortex, anterior and posterior cingulate cortex, raphe, amygdala, hippocampus and striatum). We tested whether the LV 1B was associated with amygdala, striatal and prefrontal reactivity to provocations, adjusting for age, injected mass and group. Across participants, LV 1B was statistically significantly positively associated with amygdala (p = 0.01) but not with striatal (p = 0.2) or prefrontal reactivity to provocations (p = 0.3). These findings provide novel evidence that 5-HT 1B R levels are linked to amygdala reactivity to provocations in a cohort of men displaying a wide range of aggressive behavior. The data suggest that 5-HT 1B R represents an intriguing target for reducing excessive neural reactivity to provocations and thereby putatively violent behavior.
-
anterior cingulate Serotonin 1B Receptor binding is associated with emotional response inhibition
Journal of Psychiatric Research, 2017Co-Authors: Sofi Da Cunhabang, Liv V Hjordt, Dea S Stenbaek, Dorte Sestoft, Gitte M KnudsenAbstract:Abstract Serotonin has a well-established role in emotional processing and is a key neurotransmitter in impulsive aggression, presumably by facilitating response inhibition and regulating subcortical reactivity to aversive stimuli. In this study 44 men, of whom 19 were violent offenders and 25 were non-offender controls, completed an emotional Go/NoGo task requiring inhibition of prepotent motor responses to emotional facial expressions. We also measured cerebral Serotonin 1B Receptor (5-HT 1B R) binding with [ 11 C]AZ10419369 positron emission tomography within regions of the frontal cortex. We hypothesized that 5-HT 1B R would be positively associated with false alarms (failures to inhibit nogo responses) in the context of aversive (angry and fearful) facial expressions. Across groups, we found that frontal cortex 5-HT 1B R binding was positively correlated with false alarms when angry faces were go stimuli and neutral faces were nogo stimuli (p = 0.05, corrected alpha = 0.0125), but not with false alarms for non-emotional stimuli (failures to inhibit geometric figures). A posthoc analysis revealed the strongest association in anterior cingulate cortex (p = 0.006). In summary, 5-HT 1B Rs in the anterior cingulate are involved in withholding a prepotent response in the context of angry faces. Our findings suggest that Serotonin modulates response inhibition in the context of certain emotional stimuli.
-
Serotonin 1B Receptor binding is associated with trait anger and level of psychopathy in violent offenders
Biological Psychiatry, 2017Co-Authors: Sofi Da Cunhabang, Liv V Hjordt, Dorte Sestoft, Erik Perfalk, Vincent Beliveau, Camilla Bock, Szabolcs Lehel, Carsten Thomsen, Claus Svarer, Gitte M KnudsenAbstract:Abstract Background The involvement of Serotonin in aggression has traditionally been attributed to impaired prefrontal serotonergic inhibitory control of emotional reactions to provocations in antisocial individuals. However, it is unclear which specific serotonergic Receptors are involved in the effects. A large body of preclinical research supports a specific role of Serotonin 1B Receptors (5-HT 1B Rs) in aggression and impulsivity, but this has never been evaluated in humans. Methods Nineteen incarcerated violent offenders and 24 healthy control nonoffenders were included and examined with positron emission tomography, using the radioligand [ 11 C]AZ10419369 for quantification of cerebral 5-HT 1B R binding in three regions of interest: the anterior cingulate cortex, orbitofrontal cortex, and striatum. Results Group status significantly moderated the association between striatal 5-HT 1B Rs and trait anger (difference in slopes, p corrected = .04). In the violent offender group, striatal 5-HT 1B R binding was positively correlated with self-reported trait anger ( p = .0004), trait psychopathy ( p = .008), and level of psychopathy according to the Psychopathy Checklist-Revised ( p = .02). We found no group differences in 5-HT 1B R binding. Conclusions Our data demonstrate for the first time in humans a specific involvement of 5-HT 1B R binding in anger and psychopathy. 5-HT 1B Rs putatively represent a molecular target for development of pharmacologic antiaggressive treatments.
-
Fenfluramine Reduces [11C]Cimbi-36 Binding to the 5-HT2A Receptor in the Nonhuman Primate Brain.
The International Journal of Neuropsychopharmacology, 2017Co-Authors: Kai-chun Yang, Gitte M Knudsen, Christer Halldin, Vladimir Stepanov, Stefan Martinsson, Anders Ettrup, Akihiro Takano, Lars Farde, Sjoerd J. FinnemaAbstract:Background: [11C]Cimbi-36 is a Serotonin 2A Receptor agonist positron emission tomography radioligand that has recently been examined in humans. The binding of agonist radioligand is expected to be more sensitive to endogenous neurotransmitter concentrations than antagonist radioligands. In the current study, we compared the effect of Serotonin releaser fenfluramine on the binding of [11C]Cimbi-36, [11C]MDL 100907 (a Serotonin 2A Receptor antagonist radioligand), and [11C]AZ10419369 (a Serotonin 1B Receptor partial agonist radioligand with established Serotonin sensitivity) in the monkey brain. Methods: Eighteen positron emission tomography measurements, 6 for each radioligand, were performed in 3 rhesus monkeys before or after administration of 5.0 mg/kg fenfluramine. Binding potential values were determined with the simplified reference tissue model using cerebellum as the reference region. Results: Fenfluramine significantly decreased [11C]Cimbi-36 (26-62%) and [11C]AZ10419369 (35-58%) binding potential values in most regions (P < 0.05). Fenfluramine-induced decreases in [11C]MDL 100907 binding potential were 8% to 30% and statistically significant in 3 regions. Decreases in [11C]Cimbi-36 binding potential were larger than for [11C]AZ10419369 in neocortical and limbic regions (~35%) but smaller in striatum and thalamus (~40%). Decreases in [11C]Cimbi-36 binding potential were 0.9 to 2.8 times larger than for [11C]MDL 100907, and the fraction of Serotonin 2A Receptor in the high-affinity state was estimated as 54% in the neocortex. Conclusions: The Serotonin sensitivity of Serotonin 2A Receptor agonist radioligand [11C]Cimbi-36 was higher than for antagonist radioligand [11C]MDL 100907. The Serotonin sensitivity of [11C]Cimbi-36 was similar to [11C]AZ10419369, which is one of the most sensitive radioligands. [11C]Cimbi-36 is a promising radioligand to examine Serotonin release in the primate brain.
Catherine Belzung - One of the best experts on this subject based on the ideXlab platform.
-
upregulated sirtuin 5 gene expression in frontal cortex of Serotonin 1B Receptor knock out mice
Molecular Psychiatry, 2007Co-Authors: Etienne Sibille, J Su, Samuel Leman, A Le M Guisquet, Yadira Ibarguenvargas, Jennifer Joeyenwaldorf, Christin Glorioso, George C Tseng, Michael A Pezzone, Catherine BelzungAbstract:Upregulated sirtuin 5 gene expression in frontal cortex of Serotonin 1B Receptor knock out mice
-
absence of cocaine induced place conditioning in Serotonin 1B Receptor knock out mice
Pharmacology Biochemistry and Behavior, 2000Co-Authors: Catherine Belzung, K Scearcelevie, S BarreauAbstract:Abstract Absence of cocaine-induced place conditioning in Serotonin 1B Receptor knock-out mice . PHARMACOL BIOCHEM BEHAV 66 (1) 221–225, 2000.—A large body of evidence suggests that genetic factors may affect the reinforcing properties of drugs of abuse. This study investigated the involvement of the Serotonin 1B (5-HT1B) Receptor in modulating cocaine-induced place conditioning by comparing the response of 5-HT1B Receptor gene knock-out mice with wild type 129/Sv-ter mice. The rewarding effects of various doses of cocaine (0, 2.5, 5, 10, 20, and 40 mg/kg) were examined in both strains. Results clearly show that 5-HT1B Receptor knock-out mice failed to display a conditioned place preference for stimuli paired with cocaine while wild type mice exhibited a conditioned place preference for the compartment paired with cocaine (5 and 20 mg/kg). As other studies showed that 5-HT1B knock-out mice self-administer cocaine, these results suggest a dissociation between the psychologic state linked to self-administration and the one measured in conditioned place preference.
Mikael Tiger - One of the best experts on this subject based on the ideXlab platform.
-
A randomized placebo-controlled PET study of ketamine´s effect on Serotonin 1B Receptor binding in patients with SSRI-resistant depression
Translational Psychiatry, 2020Co-Authors: Mikael Tiger, Emma R. Veldman, Per Svenningsson, Carl Johan Ekman, Christer Halldin, Johan LundbergAbstract:The glutamate N-methyl-d-aspartate Receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the Serotonin (5-HT)1B Receptor. Low 5-HT1B Receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT1B Receptor binding in the ventral striatum (VST) has been demonstrated after ketamine infusion. Thirty selective Serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT1B Receptor selective radioligand [11C]AZ10419369 and positron emission tomography (PET) before and 24–72 h after treatment. 5-HT1B Receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT1B Receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT1B Receptor binding in VST at baseline correlated with MDD symptom ratings (r = −0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = −0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT1B Receptor binding in VST. Further studies examining the role of 5-HT1B Receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT1B Receptor as an MDD treatment response marker.
-
a randomized placebo controlled pet study of ketamine s effect on Serotonin 1B Receptor binding in patients with ssri resistant depression
Translational Psychiatry, 2020Co-Authors: Mikael Tiger, Emma R. Veldman, Per Svenningsson, Carl Johan Ekman, Christer Halldin, J M LundbergAbstract:The glutamate N-methyl-d-aspartate Receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the Serotonin (5-HT)1B Receptor. Low 5-HT1B Receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT1B Receptor binding in the ventral striatum (VST) has been demonstrated after ketamine infusion. Thirty selective Serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT1B Receptor selective radioligand [11C]AZ10419369 and positron emission tomography (PET) before and 24–72 h after treatment. 5-HT1B Receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT1B Receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT1B Receptor binding in VST at baseline correlated with MDD symptom ratings (r = −0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = −0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT1B Receptor binding in VST. Further studies examining the role of 5-HT1B Receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT1B Receptor as an MDD treatment response marker.
-
The 5-HT_1B Receptor - a potential target for antidepressant treatment
Psychopharmacology, 2018Co-Authors: Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan LundbergAbstract:Major depressive disorder (MDD) is the leading cause of disability worldwide. The Serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic Serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between Serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory Receptors such as the Serotonin 1B Receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the Receptor. The last extensive review of 5-HT1BR in the pathophysiology of depression was published 2009, and based mainly on findings from animal studies. Since then, selective radioligands for in vivo quantification of brain 5-HT1BR binding with positron emission tomography has been developed, providing new knowledge on the role of 5-HT1BR in MDD and its treatment. The main focus of this review is the role of 5-HT1BR in relation to MDD and its treatment, although studies of 5-HT1BR in obsessive-compulsive disorder, alcohol dependence, and cocaine dependence are also reviewed. The evidence outlined range from animal models of disease, effects of 5-HT1B Receptor agonists and antagonists, case-control studies of 5-HT1B Receptor binding postmortem and in vivo, with positron emission tomography, to clinical studies of 5-HT1B Receptor effects of established treatments for MDD. Low 5-HT1BR binding in limbic regions has been found in MDD patients. When 5-HT1BR ligands are administered to animals, 5-HT1BR agonists most consistently display antidepressant-like properties, though it is not yet clear how 5-HT1BR is best approached for optimal MDD treatment.
-
The 5-HT1B Receptor - a potential target for antidepressant treatment.
Psychopharmacology, 2018Co-Authors: Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan LundbergAbstract:Major depressive disorder (MDD) is the leading cause of disability worldwide. The Serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic Serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between Serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory Receptors such as the Serotonin 1B Receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the Receptor. The last extensive review of 5-HT1BR in the pathophysiology of depression was published 2009, and based mainly on findings from animal studies. Since then, selective radioligands for in vivo quantification of brain 5-HT1BR binding with positron emission tomography has been developed, providing new knowledge on the role of 5-HT1BR in MDD and its treatment. The main focus of this review is the role of 5-HT1BR in relation to MDD and its treatment, although studies of 5-HT1BR in obsessive-compulsive disorder, alcohol dependence, and cocaine dependence are also reviewed. The evidence outlined range from animal models of disease, effects of 5-HT1B Receptor agonists and antagonists, case-control studies of 5-HT1B Receptor binding postmortem and in vivo, with positron emission tomography, to clinical studies of 5-HT1B Receptor effects of established treatments for MDD. Low 5-HT1BR binding in limbic regions has been found in MDD patients. When 5-HT1BR ligands are administered to animals, 5-HT1BR agonists most consistently display antidepressant-like properties, though it is not yet clear how 5-HT1BR is best approached for optimal MDD treatment.
Liv V Hjordt - One of the best experts on this subject based on the ideXlab platform.
-
men with high Serotonin 1B Receptor binding respond to provocations with heightened amygdala reactivity
NeuroImage, 2018Co-Authors: Sofi Da Cunhabang, Liv V Hjordt, Patrick M Fisher, Erik Perfalk, Vincent Beliveau, Klaus K Holst, Gitte M KnudsenAbstract:Abstract Serotonin signalling influences amygdala reactivity to threat-related emotional facial expressions in healthy adults, but in vivo Serotonin signalling has never been investigated in the context of provocative stimuli in aggressive individuals. The aim of this study was to evaluate associations between Serotonin 1B Receptor (5-HT 1B R) levels and brain reactivity to provocations. We quantified regional 5-HT 1B R binding using [ 11 C]AZ10419369 positron emission tomography (PET) and measured brain activation following provocations with functional magnetic resonance imaging (fMRI) in eighteen violent offenders and 25 healthy control subjects. The point-subtraction aggression paradigm (PSAP) was used in fMRI to elicit provocations in terms of monetary subtractions from a fictive opponent. We estimated global 5-HT 1B R binding using a linear structural equation model, with a single latent response variable (LV 1B ) modelling shared correlation between 5-HT 1B R binding across multiple brain regions (neocortex, anterior and posterior cingulate cortex, raphe, amygdala, hippocampus and striatum). We tested whether the LV 1B was associated with amygdala, striatal and prefrontal reactivity to provocations, adjusting for age, injected mass and group. Across participants, LV 1B was statistically significantly positively associated with amygdala (p = 0.01) but not with striatal (p = 0.2) or prefrontal reactivity to provocations (p = 0.3). These findings provide novel evidence that 5-HT 1B R levels are linked to amygdala reactivity to provocations in a cohort of men displaying a wide range of aggressive behavior. The data suggest that 5-HT 1B R represents an intriguing target for reducing excessive neural reactivity to provocations and thereby putatively violent behavior.
-
anterior cingulate Serotonin 1B Receptor binding is associated with emotional response inhibition
Journal of Psychiatric Research, 2017Co-Authors: Sofi Da Cunhabang, Liv V Hjordt, Dea S Stenbaek, Dorte Sestoft, Gitte M KnudsenAbstract:Abstract Serotonin has a well-established role in emotional processing and is a key neurotransmitter in impulsive aggression, presumably by facilitating response inhibition and regulating subcortical reactivity to aversive stimuli. In this study 44 men, of whom 19 were violent offenders and 25 were non-offender controls, completed an emotional Go/NoGo task requiring inhibition of prepotent motor responses to emotional facial expressions. We also measured cerebral Serotonin 1B Receptor (5-HT 1B R) binding with [ 11 C]AZ10419369 positron emission tomography within regions of the frontal cortex. We hypothesized that 5-HT 1B R would be positively associated with false alarms (failures to inhibit nogo responses) in the context of aversive (angry and fearful) facial expressions. Across groups, we found that frontal cortex 5-HT 1B R binding was positively correlated with false alarms when angry faces were go stimuli and neutral faces were nogo stimuli (p = 0.05, corrected alpha = 0.0125), but not with false alarms for non-emotional stimuli (failures to inhibit geometric figures). A posthoc analysis revealed the strongest association in anterior cingulate cortex (p = 0.006). In summary, 5-HT 1B Rs in the anterior cingulate are involved in withholding a prepotent response in the context of angry faces. Our findings suggest that Serotonin modulates response inhibition in the context of certain emotional stimuli.
-
Serotonin 1B Receptor binding is associated with trait anger and level of psychopathy in violent offenders
Biological Psychiatry, 2017Co-Authors: Sofi Da Cunhabang, Liv V Hjordt, Dorte Sestoft, Erik Perfalk, Vincent Beliveau, Camilla Bock, Szabolcs Lehel, Carsten Thomsen, Claus Svarer, Gitte M KnudsenAbstract:Abstract Background The involvement of Serotonin in aggression has traditionally been attributed to impaired prefrontal serotonergic inhibitory control of emotional reactions to provocations in antisocial individuals. However, it is unclear which specific serotonergic Receptors are involved in the effects. A large body of preclinical research supports a specific role of Serotonin 1B Receptors (5-HT 1B Rs) in aggression and impulsivity, but this has never been evaluated in humans. Methods Nineteen incarcerated violent offenders and 24 healthy control nonoffenders were included and examined with positron emission tomography, using the radioligand [ 11 C]AZ10419369 for quantification of cerebral 5-HT 1B R binding in three regions of interest: the anterior cingulate cortex, orbitofrontal cortex, and striatum. Results Group status significantly moderated the association between striatal 5-HT 1B Rs and trait anger (difference in slopes, p corrected = .04). In the violent offender group, striatal 5-HT 1B R binding was positively correlated with self-reported trait anger ( p = .0004), trait psychopathy ( p = .008), and level of psychopathy according to the Psychopathy Checklist-Revised ( p = .02). We found no group differences in 5-HT 1B R binding. Conclusions Our data demonstrate for the first time in humans a specific involvement of 5-HT 1B R binding in anger and psychopathy. 5-HT 1B Rs putatively represent a molecular target for development of pharmacologic antiaggressive treatments.
Johan Lundberg - One of the best experts on this subject based on the ideXlab platform.
-
A randomized placebo-controlled PET study of ketamine´s effect on Serotonin 1B Receptor binding in patients with SSRI-resistant depression
Translational Psychiatry, 2020Co-Authors: Mikael Tiger, Emma R. Veldman, Per Svenningsson, Carl Johan Ekman, Christer Halldin, Johan LundbergAbstract:The glutamate N-methyl-d-aspartate Receptor antagonist ketamine has a rapid antidepressant effect. Despite large research efforts, ketamine’s mechanism of action in major depressive disorder (MDD) has still not been determined. In rodents, the antidepressant properties of ketamine were found to be dependent on both the α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and the Serotonin (5-HT)1B Receptor. Low 5-HT1B Receptor binding in limbic brain regions is a replicated finding in MDD. In non-human primates, AMPA-dependent increase in 5-HT1B Receptor binding in the ventral striatum (VST) has been demonstrated after ketamine infusion. Thirty selective Serotonin reuptake inhibitor-resistant MDD patients were recruited via advertisement and randomized to double-blind monotherapy with 0.5 mg/kg ketamine or placebo infusion. The patients were examined with the 5-HT1B Receptor selective radioligand [11C]AZ10419369 and positron emission tomography (PET) before and 24–72 h after treatment. 5-HT1B Receptor binding did not significantly alter in patients treated with ketamine compared with placebo. An increase in 5-HT1B Receptor binding with 16.7 % (p = 0.036) was found in the hippocampus after one ketamine treatment. 5-HT1B Receptor binding in VST at baseline correlated with MDD symptom ratings (r = −0.426, p = 0.019) and with reduction of depressive symptoms with ketamine (r = −0.644, p = 0.002). In conclusion, reduction of depressive symptoms in MDD patients after ketamine treatment is correlated inversely with baseline 5-HT1B Receptor binding in VST. Further studies examining the role of 5-HT1B Receptors in the antidepressant mechanism of action of ketamine should be conducted, homing in on the 5-HT1B Receptor as an MDD treatment response marker.
-
The 5-HT_1B Receptor - a potential target for antidepressant treatment
Psychopharmacology, 2018Co-Authors: Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan LundbergAbstract:Major depressive disorder (MDD) is the leading cause of disability worldwide. The Serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic Serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between Serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory Receptors such as the Serotonin 1B Receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the Receptor. The last extensive review of 5-HT1BR in the pathophysiology of depression was published 2009, and based mainly on findings from animal studies. Since then, selective radioligands for in vivo quantification of brain 5-HT1BR binding with positron emission tomography has been developed, providing new knowledge on the role of 5-HT1BR in MDD and its treatment. The main focus of this review is the role of 5-HT1BR in relation to MDD and its treatment, although studies of 5-HT1BR in obsessive-compulsive disorder, alcohol dependence, and cocaine dependence are also reviewed. The evidence outlined range from animal models of disease, effects of 5-HT1B Receptor agonists and antagonists, case-control studies of 5-HT1B Receptor binding postmortem and in vivo, with positron emission tomography, to clinical studies of 5-HT1B Receptor effects of established treatments for MDD. Low 5-HT1BR binding in limbic regions has been found in MDD patients. When 5-HT1BR ligands are administered to animals, 5-HT1BR agonists most consistently display antidepressant-like properties, though it is not yet clear how 5-HT1BR is best approached for optimal MDD treatment.
-
The 5-HT1B Receptor - a potential target for antidepressant treatment.
Psychopharmacology, 2018Co-Authors: Mikael Tiger, Katarina Varnäs, Yoshiro Okubo, Johan LundbergAbstract:Major depressive disorder (MDD) is the leading cause of disability worldwide. The Serotonin hypothesis may be the model of MDD pathophysiology with the most support. The majority of antidepressants enhance synaptic Serotonin levels quickly, while it usually takes weeks to discern MDD treatment effect. It has been hypothesized that the time lag between Serotonin increase and reduction of MDD symptoms is due to downregulation of inhibitory Receptors such as the Serotonin 1B Receptor (5-HT1BR). The research on 5-HT1BR has previously been hampered by a lack of selective ligands for the Receptor. The last extensive review of 5-HT1BR in the pathophysiology of depression was published 2009, and based mainly on findings from animal studies. Since then, selective radioligands for in vivo quantification of brain 5-HT1BR binding with positron emission tomography has been developed, providing new knowledge on the role of 5-HT1BR in MDD and its treatment. The main focus of this review is the role of 5-HT1BR in relation to MDD and its treatment, although studies of 5-HT1BR in obsessive-compulsive disorder, alcohol dependence, and cocaine dependence are also reviewed. The evidence outlined range from animal models of disease, effects of 5-HT1B Receptor agonists and antagonists, case-control studies of 5-HT1B Receptor binding postmortem and in vivo, with positron emission tomography, to clinical studies of 5-HT1B Receptor effects of established treatments for MDD. Low 5-HT1BR binding in limbic regions has been found in MDD patients. When 5-HT1BR ligands are administered to animals, 5-HT1BR agonists most consistently display antidepressant-like properties, though it is not yet clear how 5-HT1BR is best approached for optimal MDD treatment.
-
Distribution and levels of 5-HT1B Receptors in anterior cingulate cortex of patients with bipolar disorder, major depressive disorder and schizophrenia – An autoradiography study
European Neuropsychopharmacology, 2017Co-Authors: Emma R. Veldman, Marie Svedberg, Per Svenningsson, Johan LundbergAbstract:The Serotonin 1B Receptor has recently received more interest as a possible new target for pharmacological treatment of psychiatric disorders. However, the exact mechanisms of action remain unclear. This study aimed to examine the binding distribution and levels of the Serotonin 1B Receptor in-depth in the anterior cingulate cortex (ACC) and provide more insight in its functional role in bipolar disorder (BD), major depressive disorder (MDD) and schizophrenia (SZ). Serotonin 1B Receptor binding distribution was visualized with high resolution autoradiography (ARG), using the radioligand [3H]AZ10419369, in postmortem ACC tissue from patients diagnosed with BD (n=14), MDD (n=12), SZ (n=13) and healthy subjects (n=13). Moreover, a quantification of Receptor binding was made with ARG, in relation to patient group, age and gender. In all subject groups a significantly higher specific binding of Serotonin 1B Receptor was measured in the outer ACC layers compared to the inner ACC layers. Correlation analysis with ARG binding patterns of several radioligands resulted in a significant correlation with glutamatergic N-methyl-D-aspartate Receptor binding in the outer layers. No significant difference was found between subject groups in binding levels and distribution. In female subjects a significantly lower Receptor binding was found than in male subjects, which was most profound in patients diagnosed with MDD. The binding distribution of the Serotonin 1B Receptor found in this study supports a role in glutamate transmission in the ACC and was not shown to be significantly altered in BD, MDD or SZ. A gender difference in Serotonin 1B Receptor binding was found.
