Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats

Stanisavljević, Andrijana; Perić, Ivana; Gass, Peter; Inta, Dragoš; Lang, Undine E.; Borgwardt, Stefan; Filipović, Dragana

doi:10.1016/j.neuroscience.2018.11.015

Cited by 29 publications

(19 citation statements)

References 66 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A possible explanation for this increase may be that c-Fos protein is stimulated by an increased concentration of ROS, which in turn leads the cell to a state of oxidative stress and activates transcription factors ( Phull et al, 2018 ). A second possibility would be that c-Fos can be stimulated through the activation of the NMDA glutamatergic receptor and Ca 2+ channels ( Stanisavljevic et al, 2019 ). These receptors can bind to another metabotropic receptor, such as dopaminergic D1R.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, stress can lead to mitochondrial dysfunction, resulting in an increased concentration of ROS and leading to a state of oxidative stress. These reactive oxygen species can stimulate the activation of nuclear proteins and genes that act as transcription factors, as is the case with the c-Fos protein ( Phull et al, 2018 ; Stanisavljevic et al, 2019 ).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior

Felippe

Oliveira

Barbosa

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

Aggression is defined as hostile behavior that results in psychological damage, injury and even death among individuals. When aggression presents itself in an exacerbated and constant way, it can be considered escalating or pathological. The association between social stress and the emergence of exacerbated aggressiveness is common and is suggested to be interconnected through very complex neurobiological factors. For example, alterations in the expression of the dopaminergic receptors D1 and D2, reactive oxygen species (ROS) and the c-Fos protein in the cortex have been observed. Our objective was to analyze which factors are involved at the neurobiological level in the highly aggressive response of Swiss Webster adult male mice in a vivarium. In this work, we investigated the relationship among dopaminergic receptors, the production of ROS and the expression of c-Fos. Mice with exacerbated aggression were identified by the model of spontaneous aggression (MSA) based on the grouping of young mice and the regrouping of the same animals in adulthood. During the regrouping, we observed different categories of behavior resulting from social stress, such as (i) highly aggressive animals, (ii) defeated animals, and (iii) harmonic groups. To evaluate the dopaminergic system and the c-Fos protein, we quantified the expression of D1 and D2 dopaminergic receptors by Western blotting and fluorescence immunohistochemistry and that of the c-Fos protein by fluorescence immunohistochemistry. The possible production of ROS was also evaluated through the dihydroethidium (DHE) assay. The results showed that aggressive and subordinate mice showed a reduction in the expression of the D1 receptor, and no significant difference in the expression of the D2 receptor was observed between the groups. In addition, aggressive mice exhibited increased production of ROS and c-Fos protein. Based on our results, we suggest that exacerbated aggression is associated with social stress, dysregulation of the dopaminergic system and exacerbated ROS production, which leads to a state of cellular oxidative stress. The overexpression of c-Fos due to social stress suggests an attempt by the cell to produce antioxidant agents to reduce the toxic cellular concentration of ROS.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior

Felippe

Oliveira

Barbosa

et al. 2021

Front. Cell. Neurosci.

View full text Add to dashboard Cite

show abstract

“…The antipsychotic olanzapine reduces anxiety-like behaviors in socially isolated rats while concomitantly increasing c-Fos expression in the amygdala. 87 The prosocial entactogen, 5-HT releasing drug methylenedioxymethamphetamine (MDMA), increases c-Fos expression in the amygdala, an effect blocked by antagonists of 5-HT 1A Rs. 88 Also, a selective, postsynaptic 5-HT 1A R agonist dose-dependently increases c-Fos in several neural systems in the rat brain, though analysis of the amygdala was not reported.…”

Section: ■ Discussionmentioning

confidence: 99%

(S)-5-(2′-Fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, a Serotonin Receptor Modulator, Possesses Anticonvulsant, Prosocial, and Anxiolytic-like Properties in an Fmr1 Knockout Mouse Model of Fragile X Syndrome and Autism Spectrum Disorder

Armstrong

Casey

Saraf

et al. 2020

ACS Pharmacol. Transl. Sci.

View full text Add to dashboard Cite

Fragile X syndrome (FXS) is a neurodevelopmental disorder characterized by intellectual disabilities and a plethora of neuropsychiatric symptoms. FXS is the leading monogenic cause of autism spectrum disorder (ASD), which is defined clinically by repetitive and/or restrictive patterns of behavior and social communication deficits. Epilepsy and anxiety are also common in FXS and ASD. Serotonergic neurons directly innervate and modulate the activity of neurobiological circuits altered in both disorders, providing a rationale for investigating serotonin receptors (5-HTRs) as targets for FXS and ASD drug discovery. Previously we unveiled an orally active aminotetralin, (S)-5-(2'-fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine (FPT), that exhibits partial agonist activity at 5-HT1ARs, 5-HT2CRs, and 5-HT7Rs and that reduces repetitive behaviors and increases social approach behavior in wild-type mice. Here we report that in an Fmr1 knockout mouse model of FXS and ASD, FPT is prophylactic for audiogenic seizures. No FPT-treated mice displayed audiogenic seizures, compared to 73% of vehicle-treated mice. FPT also exhibits anxiolytic-like effects in several assays and increases social interactions in both Fmr1 knockout and wild-type mice. Furthermore, FPT increases c-Fos expression in the basolateral amygdala, which is a preclinical effect produced by anxiolytic medications. Receptor pharmacology assays show that FPT binds competitively and possesses rapid association and dissociation kinetics at 5-HT1ARs and 5-HT7Rs, yet has slow association and rapid dissociation kinetics at 5-HT2CRs. Finally, we reassessed and report FPT’s affinity and function at 5-HT1ARs, 5-HT2CRs, and 5-HT7Rs. Collectively, these observations provide mounting support for further development of FPT as a pharmacotherapy for common neuropsychiatric symptoms in FXS and ASD.

show abstract

“…With this respect, different preclinical studies have demonstrated that pharmacological intervention with AAPDs is effective in ameliorating several alterations produced by adult chronic stress. It has been reported that the treatment of adult rats with olanzapine for 3 weeks can reverse depression- and anxiety-like behaviors observed following social isolation, as well as to prevent the stress-induced increase in c-Fos expression in different brain regions [ 132 ]. On the other end, chronic treatment with clozapine can revert the social isolation-induced deficits in the number of parvalbumin-positive interneurons within specific hippocampal sub-fields, thus exerting a protective effect from the deleterious effects of stress [ 133 ].…”

Section: Atypical Antipsychotic Drugs and Stress-related Mechanismmentioning

confidence: 99%

Anti-stress Properties of Atypical Antipsychotics

Sanson

Riva

2020

Pharmaceuticals

View full text Add to dashboard Cite

Stress exposure represents a major environmental risk factor for schizophrenia and other psychiatric disorders, as it plays a pivotal role in the etiology as well as in the manifestation of disease symptomatology. It may be inferred that pharmacological treatments must be able to modulate the behavioral, functional, and molecular alterations produced by stress exposure to achieve significant clinical outcomes. This review aims at examining existing clinical and preclinical evidence that supports the ability of atypical antipsychotic drugs (AAPDs) to modulate stress-related alterations. Indeed, while the pharmacodynamic differences between AAPDs have been extensively characterized, less is known on their ability to regulate downstream mechanisms that are critical for functional recovery and patient stabilization. We will discuss stress-related mechanisms, spanning from neuroendocrine function to inflammation and neuronal plasticity, which are relevant for the manifestation of schizophrenic symptomatology, and we will discuss if and how AAPDs may interfere with such mechanisms. Considering the impact of stress in everyday life, we believe that a better understanding of the potential effects of AAPDs on stress-related mechanisms may provide novel and important insights for improving therapeutic strategies aimed at promoting coping mechanisms and enhancing the quality of life of patients affected by psychiatric disorders.

show abstract

Brain Sub/Region-Specific Effects of Olanzapine on c-Fos Expression of Chronically Socially Isolated Rats

Cited by 29 publications

References 66 publications

Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior

Experimental Social Stress: Dopaminergic Receptors, Oxidative Stress, and c-Fos Protein Are Involved in Highly Aggressive Behavior

(S)-5-(2′-Fluorophenyl)-N,N-dimethyl-1,2,3,4-tetrahydronaphthalen-2-amine, a Serotonin Receptor Modulator, Possesses Anticonvulsant, Prosocial, and Anxiolytic-like Properties in an Fmr1 Knockout Mouse Model of Fragile X Syndrome and Autism Spectrum Disorder

Anti-stress Properties of Atypical Antipsychotics

Contact Info

Product

Resources

About