The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Daniel G Ehlinger - One of the best experts on this subject based on the ideXlab platform.
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cav1 2 l type calcium channels regulate stress Coping Behavior via serotonin neurons
Neuropharmacology, 2019Co-Authors: Daniel G Ehlinger, Kathryn G CommonsAbstract:Abstract Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through which CACNA1C and Cav1.2 LTCCs impact disease etiology. However, serotonin (5-HT) neurotransmission has been consistently implicated in these neuropsychiatric disorders and Cav1.2 LTCCs may influence 5-HT neuron activity during relevant Behavioral states such as stress. We utilized a temporally controlled and 5-HT neuron specific Cacna1c knockout mouse model to assess stress-Coping Behavior using the forced swim test and dorsal raphe (DR) 5-HT neuron Fos activation. Furthermore, we assessed 5-HT1A receptor function and feedback inhibition of the DR following administration of the 5-HT1A antagonist WAY-100635. We find that 5-HT neuron Cacna1c knockout disrupts active-Coping Behavior in the forced swim test and that this Behavioral effect is rescued by blocking 5-HT1A receptors. Moreover, Cacna1c knockout mice display enhanced Fos expression in caudal DR 5-HT neurons and an enhanced response to a 5-HT1A receptor antagonist in rostral DR 5-HT neurons, indicating that loss of Cacna1c disrupts both 5-HT neuron activation and 5-HT1A dependent feedback inhibition across the caudal to rostral DR. Collectively, these results reveal an important role for 5-HT neuron Cav1.2 LTCCs in stress-Coping Behavior and 5-HT1A receptor function. This suggests that alterations in CACNA1C function or expression could influence the development or treatment of neuropsychiatric disorder through serotonergic mechanisms.
Nicolas Singewald - One of the best experts on this subject based on the ideXlab platform.
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conditional mouse mutants highlight mechanisms of corticotropin releasing hormone effects on stress Coping Behavior
Molecular Psychiatry, 2008Co-Authors: M A Steiner, Nigel Whittle, Annette M Vogl, S M Walser, M Ableitner, Damian Refojo, Marc Ekker, John L R Rubenstein, Gunter K Stalla, Nicolas SingewaldAbstract:Hypersecretion of central corticotropin-releasing hormone (CRH) has been implicated in the pathophysiology of affective disorders. Both, basic and clinical studies suggested that disrupting CRH signaling through CRH type 1 receptors (CRH-R1) can ameliorate stress-related clinical conditions. To study the effects of CRH-R1 blockade upon CRH-elicited Behavioral and neurochemical changes we created different mouse lines overexpressing CRH in distinct spatially restricted patterns. CRH overexpression in the entire central nervous system, but not when overexpressed in specific forebrain regions, resulted in stress-induced hypersecretion of stress hormones and increased active stress-Coping Behavior reflected by reduced immobility in the forced swim test and tail suspension test. These changes were related to acute effects of overexpressed CRH as they were normalized by CRH-R1 antagonist treatment and recapitulated the effect of stress-induced activation of the endogenous CRH system. Moreover, we identified enhanced noradrenergic activity as potential molecular mechanism underlying increased active stress-Coping Behavior observed in these animals. Thus, these transgenic mouse lines may serve as animal models for stress-elicited pathologies and treatments that target the central CRH system.
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release of oxytocin in the rat central amygdala modulates stress Coping Behavior and the release of excitatory amino acids
Neuropsychopharmacology, 2005Co-Authors: Karl Ebner, Oliver J Bosch, Simone A Kromer, Nicolas Singewald, Inga D NeumannAbstract:Release of Oxytocin in the Rat Central Amygdala Modulates Stress-Coping Behavior and the Release of Excitatory Amino Acids
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release of oxytocin in the rat central amygdala modulates stress Coping Behavior and the release of excitatory amino acids
Neuropsychopharmacology, 2005Co-Authors: Karl Ebner, Oliver J Bosch, Simone A Kromer, Nicolas Singewald, Inga D NeumannAbstract:Previous experiments have indicated that the release of oxytocin (OXT) occurs in various hypothalamic and extrahypothalamic brain areas. In the present study, we investigated in male rats whether swim stress triggers the release of OXT in the central amygdala (CeA), a key area in processing emotions and stress responses. Further, we examined the physiological significance of OXT released within the CeA for Behavioral responses during forced swimming as well as effects on the local release of selected amino acids including glutamate, aspartate, arginine, taurine, and GABA, which are thought to modulate processing of emotions. Exposure to a 10-min forced swimming session caused a significant increase in OXT release (200%, p<0.01) within, but not outside, the CeA as monitored by microdialysis. Administration of the OXT receptor antagonist des-Gly-NH2d(CH2)5(Tyr(Me)2Thr4)OVT via inverse microdialysis into the amygdala before and during exposure to swimming reduced the floating time by 55% (p<0.05) and increased the swimming time by 29% (p<0.05) indicative of a more active stress-Coping strategy. Simultaneously, local administration of the OXT receptor antagonist caused a significant increase in the stress-induced release of the excitatory amino acids glutamate and aspartate, whereas the basal release of these amino acids remained unchanged. Taken together, these findings demonstrate a significant activation of the oxytocinergic system in the CeA in response to swim stress. Furthermore, our data indicate that OXT receptor-mediated mechanisms within the amygdala are involved in the generation of passive stress-Coping strategies, which might be mediated at least in part via its inhibitory influence on the local release of excitatory amino acids during stress.
CT Wotjak - One of the best experts on this subject based on the ideXlab platform.
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Impaired cannabinoid receptor type 1 signaling interferes with stress-Coping Behavior in mice.
Pharmacogenomics J, 2008Co-Authors: CT WotjakAbstract:Dysregulation of the endocannabinoid system is known to interfere with emotional processing of stressful events. Here, we studied the role of cannabinoid receptor type 1 (CB1) signaling in stress-Coping Behaviors using the forced swim test (FST) with repeated exposures. We compared effects of genetic inactivation with pharmacological blockade of CB1 receptors both in male and female mice. In addition, we investigated potential interactions of the endocannabinoid system with monoaminergic and neurotrophin systems of the brain. Naive CB1 receptor-deficient mice (CB1-/-) showed increased passive stress-Coping Behaviors as compared to wild-type littermates (CB1+/+) in the FST, independent of sex. These findings were partially reproduced in C57BL/6N animals and fully reproduced in female CB1+/+ mice by pharmacological blockade of CB1 receptors with the CB1 receptor antagonist SR141716. The specificity of SR141716 was confirmed in female CB1-/- mice, where it failed to affect Behavioral performance. Sensitivity to the antidepressants desipramine and paroxetine was preserved, but slightly altered in female CB1-/- mice. There were no genotype differences between CB1+/+ and CB1-/- mice in monoamine oxidase A and B activities under basal conditions, nor in monoamine content of hippocampal tissue after FST exposure. mRNA expression of vesicular glutamate transporter type 1 was unaffected in CB1-/- mice, but mRNA expression of brain-derived neurotrophic factor (BDNF) was reduced in the hippocampus. Our results suggest that impaired CB1 receptor function promotes passive stress-Coping Behavior, which, at least in part, might relate to alterations in BDNF function.
Inga D Neumann - One of the best experts on this subject based on the ideXlab platform.
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the crf system mediates increased passive stress Coping Behavior following the loss of a bonded partner in a monogamous rodent
Neuropsychopharmacology, 2009Co-Authors: Oliver J Bosch, Inga D Neumann, Hemanth P Nair, Todd H Ahern, Larry J YoungAbstract:Social relationships significantly influence physiology and Behavior, including the hypothalamo–pituitary–adrenal axis, anxiety, and mental health. Disruption of social bonds through separation or death often results in profound grieving, depression, and physical illness. As the monogamous prairie vole forms enduring, selective pair bonds with the mating partner, they provide an animal model to study the physiological consequences of pair bonding and, thus, the loss of the bonded partner. Male prairie voles were paired with a novel female or male sibling. After 5 days, half of the males of each group were separated from the partner. Elevated plus-maze, forced swim, and tail suspension tests were used to assess anxiety-like and passive stress-Coping Behaviors indicative of depressive-like Behavior. Following 4 days of separation from the female but not the male partner, experimental males displayed increased passive stress-Coping. This effect was abolished by long-term intracerebroventricular infusion of a nonselective corticotropin-releasing factor (CRF) receptor antagonist without disrupting the bond itself. Both CRF type 1 and 2 receptors were involved in the emergence of passive stress-Coping Behavior. Furthermore, pairing with a female was associated with elevated CRF mRNA in the bed nucleus of the stria terminalis, and partner loss elicited a pronounced increase in circulating corticosteroid and adrenal weight. We speculate that the CRF system may mediate an aversive affect following separation from the female partner, which may facilitate proximity seeking between the pair-bonded individuals. Hence, the prairie vole model may provide insights into brain mechanisms involved in the psychopathological consequences of partner loss.
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release of oxytocin in the rat central amygdala modulates stress Coping Behavior and the release of excitatory amino acids
Neuropsychopharmacology, 2005Co-Authors: Karl Ebner, Oliver J Bosch, Simone A Kromer, Nicolas Singewald, Inga D NeumannAbstract:Release of Oxytocin in the Rat Central Amygdala Modulates Stress-Coping Behavior and the Release of Excitatory Amino Acids
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release of oxytocin in the rat central amygdala modulates stress Coping Behavior and the release of excitatory amino acids
Neuropsychopharmacology, 2005Co-Authors: Karl Ebner, Oliver J Bosch, Simone A Kromer, Nicolas Singewald, Inga D NeumannAbstract:Previous experiments have indicated that the release of oxytocin (OXT) occurs in various hypothalamic and extrahypothalamic brain areas. In the present study, we investigated in male rats whether swim stress triggers the release of OXT in the central amygdala (CeA), a key area in processing emotions and stress responses. Further, we examined the physiological significance of OXT released within the CeA for Behavioral responses during forced swimming as well as effects on the local release of selected amino acids including glutamate, aspartate, arginine, taurine, and GABA, which are thought to modulate processing of emotions. Exposure to a 10-min forced swimming session caused a significant increase in OXT release (200%, p<0.01) within, but not outside, the CeA as monitored by microdialysis. Administration of the OXT receptor antagonist des-Gly-NH2d(CH2)5(Tyr(Me)2Thr4)OVT via inverse microdialysis into the amygdala before and during exposure to swimming reduced the floating time by 55% (p<0.05) and increased the swimming time by 29% (p<0.05) indicative of a more active stress-Coping strategy. Simultaneously, local administration of the OXT receptor antagonist caused a significant increase in the stress-induced release of the excitatory amino acids glutamate and aspartate, whereas the basal release of these amino acids remained unchanged. Taken together, these findings demonstrate a significant activation of the oxytocinergic system in the CeA in response to swim stress. Furthermore, our data indicate that OXT receptor-mediated mechanisms within the amygdala are involved in the generation of passive stress-Coping strategies, which might be mediated at least in part via its inhibitory influence on the local release of excitatory amino acids during stress.
Kathryn G Commons - One of the best experts on this subject based on the ideXlab platform.
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cav1 2 l type calcium channels regulate stress Coping Behavior via serotonin neurons
Neuropharmacology, 2019Co-Authors: Daniel G Ehlinger, Kathryn G CommonsAbstract:Abstract Human genetic variation in the gene CACNA1C, which codes for the alpha-1c subunit of Cav1.2 L-type calcium channels (LTCCs), has been broadly associated with enhanced risk for neuropsychiatric disorders including major depression, bipolar and schizophrenia. Little is known about the specific neural circuits through which CACNA1C and Cav1.2 LTCCs impact disease etiology. However, serotonin (5-HT) neurotransmission has been consistently implicated in these neuropsychiatric disorders and Cav1.2 LTCCs may influence 5-HT neuron activity during relevant Behavioral states such as stress. We utilized a temporally controlled and 5-HT neuron specific Cacna1c knockout mouse model to assess stress-Coping Behavior using the forced swim test and dorsal raphe (DR) 5-HT neuron Fos activation. Furthermore, we assessed 5-HT1A receptor function and feedback inhibition of the DR following administration of the 5-HT1A antagonist WAY-100635. We find that 5-HT neuron Cacna1c knockout disrupts active-Coping Behavior in the forced swim test and that this Behavioral effect is rescued by blocking 5-HT1A receptors. Moreover, Cacna1c knockout mice display enhanced Fos expression in caudal DR 5-HT neurons and an enhanced response to a 5-HT1A receptor antagonist in rostral DR 5-HT neurons, indicating that loss of Cacna1c disrupts both 5-HT neuron activation and 5-HT1A dependent feedback inhibition across the caudal to rostral DR. Collectively, these results reveal an important role for 5-HT neuron Cav1.2 LTCCs in stress-Coping Behavior and 5-HT1A receptor function. This suggests that alterations in CACNA1C function or expression could influence the development or treatment of neuropsychiatric disorder through serotonergic mechanisms.