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Marta Rodríguez-arias - One of the best experts on this subject based on the ideXlab platform.
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Social Defeat-induced increase in the conditioned rewarding effects of cocaine: Role of CX3CL1
Progress in neuro-psychopharmacology & biological psychiatry, 2019Co-Authors: Sandra Montagud-romero, José Miñarro, Raúl Ballestín, Jorge Montesinos, Francisco Javier Pavón, M. Carmen Blanco-gandía, Fernando Rodríguez De Fonseca, Consuelo Guerri, Marta Rodríguez-ariasAbstract:Abstract Social stress is associated with higher vulnerability to drug use, as it enhances the reinforcing effects of psychostimulants in rodents. Furthermore, continued or severe stress induces a proinflammatory state of microglial activation and augmented cytokine production. The aim of the present work was to evaluate the role of fractalkine [C-X3-C motif ligand 1 (CX3CL1)], an inflammatory chemokine, in the increased conditioned rewarding effects of cocaine in animals exposed to Social Defeat stress. In addition, we measured the signaling cascade pathway of CX3CL1 in the hippocampus (HPC) (including p-ERK/ERK, p-p38/p38 MAPK, p-p65/p65 NFκB and p-CREB/CREB ratios). The glutamate receptor subunits NR1, NR2B and GluA1 were also assessed. A total of 102 adult male C57BL/6 J wild-type (WT) and Cx3cr1 knockout (KO) mice were divided into different experimental groups according to stress condition (exploration or Social Defeat). Three weeks after the last Social Defeat, conditioned place preference (CPP) was induced by a subthreshold dose of cocaine (1 mg/kg). Brain tissue samples were taken 24 h after the CPP procedure to determine the levels of the proteins and transcription factors. Our results showed that, in WT animals, repeated Social Defeat (RSD) decreased CX3CL1 striatal levels without producing changes in the HPC. In addition, RSD induced an increase in the conditioned rewarding effects of cocaine, regardless of the genotype. After CPP induced by cocaine, Defeated Cx3cr1-deficient mice showed a decrease in the p-p65/p65 NFκB and pCREB/CREB ratio in the HPC, and an increase in the hippocampal levels of CX3CL1 and p-p38/p38 MAPK relation. In all Defeated mice, there was a decrease in the ionotropic glutamate receptor subunit NR1. In conclusion, these results suggest that the lack of CX3CL1/Cx3cr1 signaling under stress conditions induces changes in protein and transcription factors, indicating that CX3CL1 is needed to shield the response to Social Defeat.
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Correction: Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated Social Defeat
PloS one, 2018Co-Authors: Carmen Ferrer-pérez, José Miñarro, Raúl Ballestín, Tamara Escrivá-martínez, Sandra Montagud-romero, Marina D. Reguilón, Marta Rodríguez-ariasAbstract:It is well established that repeated Social Defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or Social Defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each Social Defeat or exploration episode. Three weeks after the last Social Defeat, anxiety was evaluated using an elevated plus maze paradigm. After this test, conditioned place preference (CPP) was induced by a subthreshold dose of cocaine (1 mg/kg). Biological samples were taken four hours after the first and the fourth Social Defeat, 3 weeks after the last Defeat episode, and after the CPP procedure. Plasma and brain tissue (prefrontal cortex, striatum and hippocampus) were used to determine the levels of the pro-inflammatory cytokine interleukin 6 (IL-6). Results showed an increase of peripheral and brain IL-6 levels after the first and fourth Social Defeat that was reverted three weeks later. Intraperitoneal administration of the anti-inflammatory drug indomethacin before each episode of stress prevented this enhancement of IL-6 levels and also reversed the increase in the rewarding effects of cocaine in Defeated mice. Conversely, this protective effect was not observed with respect to the anxiogenic consequences of Social stress. Our results confirm the hypothesis of a modulatory proinflammatory contribution to stress-induced vulnerability to drug abuse disorders and highlight anti-inflammatory interventions as a potential therapeutic tool to treat stress-related addiction disorders.
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Oxytocin prevents the increase of cocaine-related responses produced by Social Defeat.
Neuropharmacology, 2018Co-Authors: Carmen Ferrer-pérez, José Miñarro, Adriana Castro-zavala, Miguel Ángel Luján, Joanna Filarowska, Raúl Ballestín, Olga Valverde, Marta Rodríguez-ariasAbstract:Abstract The neuropeptide oxytocin (OXT) plays a critical role in the regulation of Social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated Social Defeat (RSD). During the Social Defeat procedure, 1 mg/kg of OXT was administered 30 min before each episode of RSD. Three weeks after the last Defeat, the effects of cocaine on the conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigms were evaluated. The influence of OXT on the levels of BDNF in the prefrontal cortex (PFC), striatum and hippocampus was also measured. Our results confirm that raising the levels of OXT during Social Defeat stress can block the long-lasting effects of this type of stress. OXT counteracts the anxiety induced by Social Defeat and modifies BDNF levels in all the structures we have studied. Moreover, OXT prevents RSD-induced increases in the motivational effects of cocaine. Administration of OXT before each Social Defeat blocked the Social Defeat-induced increment in the conditioned rewarding effects of cocaine in the CPP, favored the extinction of cocaine-associated memories in both the CPP and SA, and decreased reinstatement of cocaine-seeking behavior in the SA. In conclusion, the long-lasting effects of RSD are counteracted by administering OXT prior to stress, and changes in BDNF expression may underlie these protective effects.
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Social Defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse.
The European journal of neuroscience, 2018Co-Authors: Sandra Montagud-romero, María Del Carmen Blanco-gandía, José Miñarro, Carmen Ferrer-pérez, Raúl Ballestín, Marina D. Reguilón, Marta Rodríguez-ariasAbstract:Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to Social Defeat experiences (brief episodes of Social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which Social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how Social Defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of Social Defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the Social Defeat stress model, and will discuss challenges and future directions.
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Acute Social Defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.
Pharmacology biochemistry and behavior, 2015Co-Authors: Sandra Montagud-romero, María A. Aguilar, José Miñarro, C. Maldonado, Carmen Manzanedo, Marta Rodríguez-ariasAbstract:Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute Social Defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to Social Defeat in an agonistic encounter before each session of conditioning with 1mg/kg or 25mg/kg of cocaine. The effects of Social Defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25mg/kg. Adult mice exposed to Social Defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of Social Defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced.
José Miñarro - One of the best experts on this subject based on the ideXlab platform.
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Social Defeat-induced increase in the conditioned rewarding effects of cocaine: Role of CX3CL1
Progress in neuro-psychopharmacology & biological psychiatry, 2019Co-Authors: Sandra Montagud-romero, José Miñarro, Raúl Ballestín, Jorge Montesinos, Francisco Javier Pavón, M. Carmen Blanco-gandía, Fernando Rodríguez De Fonseca, Consuelo Guerri, Marta Rodríguez-ariasAbstract:Abstract Social stress is associated with higher vulnerability to drug use, as it enhances the reinforcing effects of psychostimulants in rodents. Furthermore, continued or severe stress induces a proinflammatory state of microglial activation and augmented cytokine production. The aim of the present work was to evaluate the role of fractalkine [C-X3-C motif ligand 1 (CX3CL1)], an inflammatory chemokine, in the increased conditioned rewarding effects of cocaine in animals exposed to Social Defeat stress. In addition, we measured the signaling cascade pathway of CX3CL1 in the hippocampus (HPC) (including p-ERK/ERK, p-p38/p38 MAPK, p-p65/p65 NFκB and p-CREB/CREB ratios). The glutamate receptor subunits NR1, NR2B and GluA1 were also assessed. A total of 102 adult male C57BL/6 J wild-type (WT) and Cx3cr1 knockout (KO) mice were divided into different experimental groups according to stress condition (exploration or Social Defeat). Three weeks after the last Social Defeat, conditioned place preference (CPP) was induced by a subthreshold dose of cocaine (1 mg/kg). Brain tissue samples were taken 24 h after the CPP procedure to determine the levels of the proteins and transcription factors. Our results showed that, in WT animals, repeated Social Defeat (RSD) decreased CX3CL1 striatal levels without producing changes in the HPC. In addition, RSD induced an increase in the conditioned rewarding effects of cocaine, regardless of the genotype. After CPP induced by cocaine, Defeated Cx3cr1-deficient mice showed a decrease in the p-p65/p65 NFκB and pCREB/CREB ratio in the HPC, and an increase in the hippocampal levels of CX3CL1 and p-p38/p38 MAPK relation. In all Defeated mice, there was a decrease in the ionotropic glutamate receptor subunit NR1. In conclusion, these results suggest that the lack of CX3CL1/Cx3cr1 signaling under stress conditions induces changes in protein and transcription factors, indicating that CX3CL1 is needed to shield the response to Social Defeat.
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Correction: Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated Social Defeat
PloS one, 2018Co-Authors: Carmen Ferrer-pérez, José Miñarro, Raúl Ballestín, Tamara Escrivá-martínez, Sandra Montagud-romero, Marina D. Reguilón, Marta Rodríguez-ariasAbstract:It is well established that repeated Social Defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or Social Defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each Social Defeat or exploration episode. Three weeks after the last Social Defeat, anxiety was evaluated using an elevated plus maze paradigm. After this test, conditioned place preference (CPP) was induced by a subthreshold dose of cocaine (1 mg/kg). Biological samples were taken four hours after the first and the fourth Social Defeat, 3 weeks after the last Defeat episode, and after the CPP procedure. Plasma and brain tissue (prefrontal cortex, striatum and hippocampus) were used to determine the levels of the pro-inflammatory cytokine interleukin 6 (IL-6). Results showed an increase of peripheral and brain IL-6 levels after the first and fourth Social Defeat that was reverted three weeks later. Intraperitoneal administration of the anti-inflammatory drug indomethacin before each episode of stress prevented this enhancement of IL-6 levels and also reversed the increase in the rewarding effects of cocaine in Defeated mice. Conversely, this protective effect was not observed with respect to the anxiogenic consequences of Social stress. Our results confirm the hypothesis of a modulatory proinflammatory contribution to stress-induced vulnerability to drug abuse disorders and highlight anti-inflammatory interventions as a potential therapeutic tool to treat stress-related addiction disorders.
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Oxytocin prevents the increase of cocaine-related responses produced by Social Defeat.
Neuropharmacology, 2018Co-Authors: Carmen Ferrer-pérez, José Miñarro, Adriana Castro-zavala, Miguel Ángel Luján, Joanna Filarowska, Raúl Ballestín, Olga Valverde, Marta Rodríguez-ariasAbstract:Abstract The neuropeptide oxytocin (OXT) plays a critical role in the regulation of Social and emotional behaviors. OXT plays a role in stress response and in drug reward, but to date no studies have evaluated its implication in the long-lasting increase of the motivational effects of cocaine induced by repeated Social Defeat (RSD). During the Social Defeat procedure, 1 mg/kg of OXT was administered 30 min before each episode of RSD. Three weeks after the last Defeat, the effects of cocaine on the conditioned place preference (CPP), locomotor sensitization and the self-administration (SA) paradigms were evaluated. The influence of OXT on the levels of BDNF in the prefrontal cortex (PFC), striatum and hippocampus was also measured. Our results confirm that raising the levels of OXT during Social Defeat stress can block the long-lasting effects of this type of stress. OXT counteracts the anxiety induced by Social Defeat and modifies BDNF levels in all the structures we have studied. Moreover, OXT prevents RSD-induced increases in the motivational effects of cocaine. Administration of OXT before each Social Defeat blocked the Social Defeat-induced increment in the conditioned rewarding effects of cocaine in the CPP, favored the extinction of cocaine-associated memories in both the CPP and SA, and decreased reinstatement of cocaine-seeking behavior in the SA. In conclusion, the long-lasting effects of RSD are counteracted by administering OXT prior to stress, and changes in BDNF expression may underlie these protective effects.
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Role of NMDA and AMPA glutamatergic receptors in the effects of Social Defeat on the rewarding properties of MDMA in mice.
The European journal of neuroscience, 2018Co-Authors: Maria P. García-pardo, José Miñarro, M. Llansola, Vicente Felipo, María A. AguilarAbstract:Exposure to Social stress alters the response to drugs of abuse of experimental animals. Changes in the glutamatergic system seem to play a role in the effects of Social Defeat stress on the rewarding properties of cocaine and amphetamine. The aim of the present study was to evaluate the involvement of N-methyl-D-aspartate (NMDA) and α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamate receptors in the effects of Social Defeat on the conditioned place preference induced by 3,4-methylenedioxymethamphetamine (MDMA). Our hypothesis was that changes in these receptors could mediate the effects of Social Defeat on MDMA reward. Young adult male mice were exposed to an episode of Social Defeat with an aggressive conspecific immediately before each conditioning session with MDMA (1.25 mg/kg, four sessions on alternating days). According to the treatment received before Defeats, six groups were used: saline, 5 or 10 mg/kg of memantine (NMDA antagonist) and 0.25, 1 or 5 mg/kg of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) (AMPA antagonist). One control group was exposed to exploration before place conditioning. In two additional Defeated and control groups, the membrane expression of NMDA and AMPA receptors was determined in the striatum and the hippocampus. Control and memantine-treated groups developed place preference, but not Defeated mice treated with saline or CNQX, suggesting that the blockade of NMDA receptors reversed the effects of Social Defeat. Social Defeat decreased the expression of several subunits of NMDA and AMPA receptors, mainly GluN1 and GluA1. These results demonstrated that glutamatergic plasticity is involved in the effects of Social Defeat stress on MDMA reward.
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Social Defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse.
The European journal of neuroscience, 2018Co-Authors: Sandra Montagud-romero, María Del Carmen Blanco-gandía, José Miñarro, Carmen Ferrer-pérez, Raúl Ballestín, Marina D. Reguilón, Marta Rodríguez-ariasAbstract:Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to Social Defeat experiences (brief episodes of Social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which Social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how Social Defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of Social Defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the Social Defeat stress model, and will discuss challenges and future directions.
Sandra Montagud-romero - One of the best experts on this subject based on the ideXlab platform.
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Social Defeat-induced increase in the conditioned rewarding effects of cocaine: Role of CX3CL1
Progress in neuro-psychopharmacology & biological psychiatry, 2019Co-Authors: Sandra Montagud-romero, José Miñarro, Raúl Ballestín, Jorge Montesinos, Francisco Javier Pavón, M. Carmen Blanco-gandía, Fernando Rodríguez De Fonseca, Consuelo Guerri, Marta Rodríguez-ariasAbstract:Abstract Social stress is associated with higher vulnerability to drug use, as it enhances the reinforcing effects of psychostimulants in rodents. Furthermore, continued or severe stress induces a proinflammatory state of microglial activation and augmented cytokine production. The aim of the present work was to evaluate the role of fractalkine [C-X3-C motif ligand 1 (CX3CL1)], an inflammatory chemokine, in the increased conditioned rewarding effects of cocaine in animals exposed to Social Defeat stress. In addition, we measured the signaling cascade pathway of CX3CL1 in the hippocampus (HPC) (including p-ERK/ERK, p-p38/p38 MAPK, p-p65/p65 NFκB and p-CREB/CREB ratios). The glutamate receptor subunits NR1, NR2B and GluA1 were also assessed. A total of 102 adult male C57BL/6 J wild-type (WT) and Cx3cr1 knockout (KO) mice were divided into different experimental groups according to stress condition (exploration or Social Defeat). Three weeks after the last Social Defeat, conditioned place preference (CPP) was induced by a subthreshold dose of cocaine (1 mg/kg). Brain tissue samples were taken 24 h after the CPP procedure to determine the levels of the proteins and transcription factors. Our results showed that, in WT animals, repeated Social Defeat (RSD) decreased CX3CL1 striatal levels without producing changes in the HPC. In addition, RSD induced an increase in the conditioned rewarding effects of cocaine, regardless of the genotype. After CPP induced by cocaine, Defeated Cx3cr1-deficient mice showed a decrease in the p-p65/p65 NFκB and pCREB/CREB ratio in the HPC, and an increase in the hippocampal levels of CX3CL1 and p-p38/p38 MAPK relation. In all Defeated mice, there was a decrease in the ionotropic glutamate receptor subunit NR1. In conclusion, these results suggest that the lack of CX3CL1/Cx3cr1 signaling under stress conditions induces changes in protein and transcription factors, indicating that CX3CL1 is needed to shield the response to Social Defeat.
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Correction: Indomethacin blocks the increased conditioned rewarding effects of cocaine induced by repeated Social Defeat
PloS one, 2018Co-Authors: Carmen Ferrer-pérez, José Miñarro, Raúl Ballestín, Tamara Escrivá-martínez, Sandra Montagud-romero, Marina D. Reguilón, Marta Rodríguez-ariasAbstract:It is well established that repeated Social Defeat stress can induce negative long-term consequences such as increased anxiety-like behavior and enhances the reinforcing effect of psychostimulants in rodents. In the current study, we evaluated how the immune system may play a role in these long-term effects of stress. A total of 148 OF1 mice were divided into different experimental groups according to stress condition (exploration or Social Defeat) and pre-treatment (saline, 5 or 10 mg/kg of the anti-inflammatory indomethacin) before each Social Defeat or exploration episode. Three weeks after the last Social Defeat, anxiety was evaluated using an elevated plus maze paradigm. After this test, conditioned place preference (CPP) was induced by a subthreshold dose of cocaine (1 mg/kg). Biological samples were taken four hours after the first and the fourth Social Defeat, 3 weeks after the last Defeat episode, and after the CPP procedure. Plasma and brain tissue (prefrontal cortex, striatum and hippocampus) were used to determine the levels of the pro-inflammatory cytokine interleukin 6 (IL-6). Results showed an increase of peripheral and brain IL-6 levels after the first and fourth Social Defeat that was reverted three weeks later. Intraperitoneal administration of the anti-inflammatory drug indomethacin before each episode of stress prevented this enhancement of IL-6 levels and also reversed the increase in the rewarding effects of cocaine in Defeated mice. Conversely, this protective effect was not observed with respect to the anxiogenic consequences of Social stress. Our results confirm the hypothesis of a modulatory proinflammatory contribution to stress-induced vulnerability to drug abuse disorders and highlight anti-inflammatory interventions as a potential therapeutic tool to treat stress-related addiction disorders.
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Social Defeat stress: Mechanisms underlying the increase in rewarding effects of drugs of abuse.
The European journal of neuroscience, 2018Co-Authors: Sandra Montagud-romero, María Del Carmen Blanco-gandía, José Miñarro, Carmen Ferrer-pérez, Raúl Ballestín, Marina D. Reguilón, Marta Rodríguez-ariasAbstract:Social interaction is known to be the main source of stress in human beings, which explains the translational importance of this research in animals. Evidence reported over the last decade has revealed that, when exposed to Social Defeat experiences (brief episodes of Social confrontations during adolescence and adulthood), the rodent brain undergoes remodeling and functional modifications, which in turn lead to an increase in the rewarding and reinstating effects of different drugs of abuse. The mechanisms by which Social stress cause changes in the brain and behavior are unknown, and so the objective of this review is to contemplate how Social Defeat stress induces long-lasting consequences that modify the reward system. First of all, we will describe the most characteristic results of the short- and long-term consequences of Social Defeat stress on the rewarding effects of drugs of abuse such as psychostimulants and alcohol. Secondly, and throughout the review, we will carefully assess the neurobiological mechanisms underlying these effects, including changes in the dopaminergic system, corticotrophin releasing factor signaling, epigenetic modifications and the neuroinflammatory response. To conclude, we will consider the advantages and disadvantages and the translational value of the Social Defeat stress model, and will discuss challenges and future directions.
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Acute Social Defeat stress increases the conditioned rewarding effects of cocaine in adult but not in adolescent mice.
Pharmacology biochemistry and behavior, 2015Co-Authors: Sandra Montagud-romero, María A. Aguilar, José Miñarro, C. Maldonado, Carmen Manzanedo, Marta Rodríguez-ariasAbstract:Stressful experiences modify activity in areas of the brain involved in the rewarding effects of psychostimulants. In the present study we evaluated the influence of acute Social Defeat (ASD) on the conditioned rewarding effects of cocaine in adolescent (PND 29-32) and adult (PND 50-53) male mice in the conditioned place preference (CPP) paradigm. Experimental mice were exposed to Social Defeat in an agonistic encounter before each session of conditioning with 1mg/kg or 25mg/kg of cocaine. The effects of Social Defeat on corticosterone levels were also evaluated. Adult mice exposed to ASD showed an increase in the conditioned reinforcing effects of cocaine. Only these mice developed cocaine-induced CPP with the subthreshold dose of cocaine, and they needed a higher number of extinction sessions for the 25mg/kg cocaine-induced CPP to be extinguished. In adolescent mice, on the other hand, ASD reduced the conditioned reinforcing effects of cocaine, since CPP was not produced with the lower dose of cocaine and was extinguished faster when they were conditioned with 25mg/kg. Adult mice exposed to Social Defeat displayed higher levels of corticosterone than their controls and adolescent mice. Our results confirm that the effect of Social Defeat stress on the acquisition and reinstatement of the CPP induced by cocaine varies depending on the age at which this stress is experienced.
Kim L. Huhman - One of the best experts on this subject based on the ideXlab platform.
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An acute Social Defeat stressor in early puberty increases susceptibility to Social Defeat in adulthood.
Hormones and behavior, 2017Co-Authors: Anna M. Rosenhauer, Katharine E. Mccann, Alisa Norvelle, Kim L. HuhmanAbstract:Abstract Syrian hamsters readily display territorial aggression. If they lose even a single agonistic encounter, however, hamsters show striking reductions in aggressive behavior and increases in submissive behavior, a distinct behavioral change that we have previously termed conditioned Defeat. This acute Social Defeat stressor is primarily psychological and is effective in both males and females. Therefore, we maintain that this procedure presents an ideal model for studying behavioral and physiological responses to Social stress. Here, we demonstrate that Social avoidance following Social Defeat is a particularly useful dependent measure because of its sensitivity and stability between sexes and across the estrous cycle. In addition, we demonstrate that peripubertal hamsters exposed to a single, 15 min Social Defeat exhibit significantly more Social avoidance 24 h later when compared with no-Defeat controls. Later, Defeated and non-Defeated hamsters display similar agonistic behavior in adulthood indicating that the peripubertal Defeat does not alter adult territorial aggression. After experiencing an additional Social Defeat in adulthood, however, the hamsters that experienced the pubertal Defeat respond to the adult Defeat with increased Social avoidance when compared with hamsters that were Defeated only in adulthood and with no-Defeat controls. These data are the first to show that a single Social Defeat in puberty increases susceptibility to later Social Defeat in both males and females.
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Copulatory and agonistic behavior in Syrian hamsters following Social Defeat.
Aggressive behavior, 2013Co-Authors: Elizabeth C. Jeffress, Kim L. HuhmanAbstract:Syrian hamsters are highly aggressive animals that reliably defend their home territory. After Social Defeat, however, hamsters no longer defend their home cage but instead display submissive and defensive behavior toward an intruder, a response that we have termed conditioned Defeat. Plasma testosterone is significantly reduced in Syrian hamsters following repeated Defeat suggesting that Social Defeat might also impair copulatory behavior. The present study aimed to determine whether copulatory behavior in male Syrian hamsters is suppressed following repeated Social Defeats and additionally whether exposure to a hormone-primed stimulus female after Social Defeat reduces the behavioral response to Defeat. Hamsters were paired with an aggressive opponent for one or nine Defeats using a resident-intruder model, while controls were placed into the empty cage of a resident aggressor. On the day after the last treatment, half of the hamsters were paired with a receptive female for 10 min. There were no significant differences in the copulatory behavior of Defeated versus non-Defeated hamsters, and the opportunity to copulate had no effect on subsequent conditioned Defeat testing, as Defeated animals displayed significantly more submissive behavior than did non-Defeated animals. The current data suggest that conditioned Defeat is not necessarily a maladaptive response to Social stress, at least in terms of reproductive behavior, but may instead represent a viable behavioral strategy adopted by losing animals following Social Defeat. Further, these data indicate that conditioned Defeat is relatively persistent and stable, as the opportunity to copulate does not reduce the subsequent display of submissive behavior. Language: en
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acute and chronic Social Defeat suppresses humoral immunity of male syrian hamsters mesocricetus auratus
Hormones and Behavior, 2001Co-Authors: Aaron M Jasnow, Kim L. Huhman, Randy J Nelson, Deborah L Drazen, Gregory E DemasAbstract:Stressors, both physical and psychological, can activate the hypothalamic-pituitary-adrenal (HPA) axis, leading to a wide range of physiological responses including increased glucocorticoid release and suppression of immune function. The majority of studies published to date have focused on the effects of physical stressors (e.g., cold exposure, electric shock) on immunity. The present study examined the role of a stressor, Social Defeat, on humoral immune function of Syrian hamsters (Mesocricetus auratus). Specifically, adult male Syrian hamsters experienced Social Defeat (i.e., exposure to a dominant animal in that animal's home cage) that was either acute (i.e., a single exposure) or chronic (i.e., daily exposures across 5 days). A control group of animals was placed in a resident's home cage without the resident animal present and did not experience Defeat. After the last encounter, blood samples were drawn and animals were subsequently injected with keyhole limpet hemocyanin (KLH). Blood samples were again taken 5 and 10 days postimmunization and serum was analyzed to determine serum cortisol and anti-KLH immunoglobulin G (IgG) concentrations. Cortisol concentrations were elevated in both acutely and chronically Defeated hamsters compared with control animals. In contrast, serum IgG concentrations were significantly reduced in both groups of Defeated hamsters compared with control animals. Collectively, these results demonstrate that both acute Social Defeat and chronic Social Defeat lead to activation of the HPA axis and suppression of humoral immune function. These data suggest that Social Defeat is an important, ecologically relevant model with which to examine stress-induced immune suppression in rodents.
Christopher A. Lowry - One of the best experts on this subject based on the ideXlab platform.
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repeated Social Defeat increases reactive emotional coping behavior and alters functional responses in serotonergic neurons in the rat dorsal raphe nucleus
Physiology & Behavior, 2011Co-Authors: Evan D Paul, Christopher A. Lowry, Matthew W Hale, Jodi L Lukkes, Mckenzie J Valentine, Derek M SarchetAbstract:Chronic stress is a vulnerability factor for a number of psychiatric disorders, including anxiety and affective disorders. Social Defeat in rats has proven to be a useful paradigm to investigate the neural mechanisms underlying physiologic and behavioral adaptation to acute and chronic stress. Previous studies suggest that serotonergic systems may contribute to the physiologic and behavioral adaptation to chronic stress, including Social Defeat in rodent models. In order to test the hypothesis that repeated Social Defeat alters the emotional behavior and the excitability of brainstem serotonergic systems implicated in control of emotional behavior, we exposed adult male rats either to home cage control conditions, acute Social Defeat, or Social Defeat followed 24 h later by a second Social Defeat encounter. We then assessed behavioral responses during Social Defeat as well as the excitability of serotonergic neurons within the dorsal raphe nucleus using immunohistochemical staining of tryptophan hydroxylase, a marker of serotonergic neurons, and the protein product of the immediate-early gene, c-fos. Repeated Social Defeat resulted in a shift away from proactive emotional coping behaviors, such as rearing (explorative escape behavior), and toward reactive emotional coping behaviors such as freezing. Both acute and repeated Defeat led to widespread increases in c-Fos expression in serotonergic neurons in the dorsal raphe nucleus. Changes in behavior following a second exposure to Social Defeat, relative to acute Defeat, were associated with decreased c-Fos expression in serotonergic neurons within the dorsal and ventral parts of the mid-rostrocaudal dorsal raphe nucleus, regions that have been implicated in 1) serotonergic modulation of fear- and anxiety-related behavior and 2) defensive behavior in conspecific aggressive encounters, respectively. These data support the hypothesis that serotonergic systems play a role in physiologic and behavioral responses to both acute and repeated Social Defeat.
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Early life experience alters behavior during Social Defeat: focus on serotonergic systems.
Neuroscience, 2005Co-Authors: Katherine L. Gardner, Kv Thrivikraman, Stafford L. Lightman, Paul M. Plotsky, Christopher A. LowryAbstract:Early life experience can have prolonged effects on neuroendocrine, autonomic, and behavioral responses to stress. The objective of this study was to investigate the effects of early life experience on behavior during Social Defeat, as well as on associated functional cellular responses in serotonergic and non-serotonergic neurons within the dorsal raphe nucleus, a structure which plays an important role in modulation of stress-related physiology and behavior. Male Long Evans rat pups were exposed to either normal animal facility rearing or 15 min or 180 min of maternal separation from postnatal days 2-14. As adults, these rats were exposed to a Social Defeat protocol. Differences in behavior were seen among the early life treatment groups during Social Defeat; rats exposed to 180 min of maternal separation from postnatal days 2-14 displayed more passive-submissive behaviors and less proactive coping behaviors. Analysis of the distribution of tryptophan hydroxylase and c-Fos-like immunoreactivity in control rats exposed to a novel cage and rats exposed to Social Defeat revealed that, independent of the early life experience, rats exposed to Social Defeat showed an increase in the number of c-Fos-like immunoreactive nuclei in serotonergic neurons in the middle and caudal parts of the dorsal dorsal raphe nucleus and caudal part of the ventral dorsal raphe nucleus, regions known to contain serotonergic neurons projecting to central autonomic and emotional motor control systems. This is the first study to show that the dorsomedial part of the mid-rostrocaudal dorsal raphe nucleus is engaged by a naturalistic stressor and supports the hypothesis that early life experience alters behavioral coping strategies during Social conflict; furthermore, this study is consistent with the hypothesis that topographically organized subpopulations of serotonergic neurons principally within the mid-rostrocaudal and caudal part of the dorsal dorsal raphe nucleus modulate stress-related physiological and behavioral responses.
