Modulation Of Emotional Processing Research Articles

DNA methylation of the Tacr2 gene in a CUMS model of depression.

Tacr2, the gene encoding the NK2 receptor, belongs to G protein-coupled receptors. Accumulating evidence has indicated that the tachykinin receptors may contribute to the pathophysiology of depression. During the last decade, some studies have shown that Tacr2 activation is involved in the modulation of emotional processes. However, the extent, to which stress impacts Tacr2 expression remains unclear. The molecular mechanisms underlying depression also remain poorly understood. In this study, we subjected adult male Sprague Dawley (SD) rats to chronic unpredictable mild stress (CUMS) to induce a depression-like phenotype. We then measured the body weight and performed the sucrose preference test, forced swimming test (FST) and open field test to detect the effects of stress on anhedonia and activity. Western blotting and real-time PCR were used to study the protein and mRNA expression levels of Tacr2, respectively, in the hypothalamus. To explore DNA methylation of the Tacr2 gene, we used methylated DNA immunoprecipitation sequencing (MeDIP-seq). Additionally, we used the bisulfite sequencing PCR (BSP) to further verify the DNA methylation levels of the Tacr2 receptor gene in rats. We found that the CUMS-sensitive rats exhibited a decrease in body weight and sucrose preference, a decrease in the distance traveled, rearing frequency and velocity in the open field test, and an increase in immobility time in the FST. Compared with the expression in the control rats, Tacr2 protein and mRNA expression in the hypothalamus significantly increased in the CUMS-sensitive rats; however, the DNA methylation levels of the Tacr2 gene were significantly lower than in the control rats. In summary, according to our findings, the stress-induced increase in Tacr2 expression in the hypothalamus correlated with a specific decrease in DNA methylation of the Tacr2 gene. These results may enrich the understanding of the pathological processes of depression and provide insights into therapeutic approaches for its treatment.

Atypical Modulations of N170 Component during Emotional Processing and Their Links to Social Behaviors in Ex-combatants.

Emotional processing (EP) is crucial for the elaboration and implementation of adaptive social strategies. EP is also necessary for the expression of social cognition and behavior (SCB) patterns. It is well-known that war contexts induce socio-emotional atypical functioning, in particular for those who participate in combats. Thus, ex-combatants represent an ideal non-clinical population to explore EP modulation and to evaluate its relation with SCB. The aim of this study was to explore EP and its relation with SCB dimensions such as empathy, theory of mind and social skills in a sample of 50 subjects, of which 30 were ex-combatants from illegally armed groups in Colombia, and 20 controls without combat experience. We adapted an Emotional Recognition Task for faces and words and synchronized it with electroencephalographic recording. Ex-combatants presented with higher assertion skills and showed more pronounced brain responses to faces than Controls. They did not show the bias toward anger observed in control participants whereby the latter group was more likely to misclassify neutral faces as angry. However, ex-combatants showed an atypical word valence processing. That is, words with different emotions yielded no differences in N170 modulations. SCB variables were successfully predicted by neurocognitive variables. Our results suggest that in ex-combatants the links between EP and SCB functions are reorganized. This may reflect neurocognitive modulations associated to chronic exposure to war experiences.

Neurostimulation du cortex préfrontal dorsolatéral : quels effets sur la symptomatologie, l’humeur et les émotions dans la dépression et la schizophrénie ?

Repetitive transcranial magnetic stimulation (rTMS) and transcranial direct current stimulation (tDCS) are noninvasive brain stimulation techniques currently used as therapeutic tools in various psychiatric conditions. Applied over the dorsolateral prefrontal cortex (DLPFC), they showed their efficacy in reducing drug-resistant symptoms in patients with major depression and in patients with schizophrenia with predominantly negative symptoms. The DLPFC is a brain structure involved in the expression of these symptoms as well as in other dysfunctional functions observed in theses conditions such as emotional processes. The goal of this review is to establish whether or not a link exists between clinical improvements and modulation of emotional processes following the stimulation of the DLPFC in both conditions. The data collected show that improved emotional processes is not linked to a clinical improvement neither in patients with depression nor in patients with negative schizophrenia. Our results suggests that although sharing common brain structures, the brain networks involved in both symptoms and in emotional processes would be separate.

Effect of parasympathetic stimulation on brain activity during appraisal of fearful expressions.

Autonomic nervous system activity is an important component of human emotion. Mental processes influence bodily physiology, which in turn feeds back to influence thoughts and feelings. Afferent cardiovascular signals from arterial baroreceptors in the carotid sinuses are processed within the brain and contribute to this two-way communication with the body. These carotid baroreceptors can be stimulated non-invasively by externally applying focal negative pressure bilaterally to the neck. In an experiment combining functional neuroimaging (fMRI) with carotid stimulation in healthy participants, we tested the hypothesis that manipulating afferent cardiovascular signals alters the central processing of emotional information (fearful and neutral facial expressions). Carotid stimulation, compared with sham stimulation, broadly attenuated activity across cortical and brainstem regions. Modulation of emotional processing was apparent as a significant expression-by-stimulation interaction within left amygdala, where responses during appraisal of fearful faces were selectively reduced by carotid stimulation. Moreover, activity reductions within insula, amygdala, and hippocampus correlated with the degree of stimulation-evoked change in the explicit emotional ratings of fearful faces. Across participants, individual differences in autonomic state (heart rate variability, a proxy measure of autonomic balance toward parasympathetic activity) predicted the extent to which carotid stimulation influenced neural (amygdala) responses during appraisal and subjective rating of fearful faces. Together our results provide mechanistic insight into the visceral component of emotion by identifying the neural substrates mediating cardiovascular influences on the processing of fear signals, potentially implicating central baroreflex mechanisms for anxiolytic treatment targets.

P.1.g.005 Serotonergic modulation of emotion processing by the mixed 5-HT1A/2A receptor agonist psilocybin reduces amygdala activation to negative stimuli – a pharmacological fMRI study

P.1.g.005 Serotonergic modulation of emotion processing by the mixed 5-HT1A/2A receptor agonist psilocybin reduces amygdala activation to negative stimuli – a pharmacological fMRI study

Sex differences in the modulation of emotional processing by expectation.

Many studies have reported sex differences in processing emotional events, the valence of which are unknown in advance. The present study examined whether women and men differ in processing emotional events when they do have such expectations. Event-related potentials were recorded when participants were presented with emotional pictures, the valence of which was either expected or unexpected. For women, the modulation effect by expectation was found on the early N2 response; for men, the effect was found on the late positive component. Implications are discussed in light of evolutionary theories.

The role of cerebellum in unipolar and bipolar depression: a review of the main neurobiological findings.

Evidences from studies on patients with overt cerebellar diseases as well as on healthy individuals suggest a possible role for the cerebellum in cognition, mood and behaviour. The aim of the present study is to review those neuroimaging studies examining the cerebellum in Bipolar Disorder (BD) and Major Depressive Disorder (MDD) and to illustrate a possible role of cerebellum in their pathophysiological mechanisms. Cellular and molecular findings from post mortem studies such as mitochondria abnormalities, brain-derived neurotrophic factor and its high affinity receptor tyrosine kinase B, transcription factor specificity protein 4, the glial fibrillary acidic protein have also been reviewed. In total 28 studies have been included in the review; among these, 12 studies were related to structural and functional neuroimaging of cerebellum in BD, 13 studies to structural and functional neuroimaging in MDD and 4 studies to cellular and molecular issues. This wealth of evidence from contemporary studies, indicating that the cerebellum (vermis in particular) is engaged in the modulation of emotional processing, provides strong support for the clinical relevance of cerebellar-limbic connections, and is in agreement with earlier clinical and electrophysiological studies that lead to the indication of the cerebellum as an "emotional pacemaker".

The endocannabinoid system and emotional processing: A pharmacological fMRI study with ∆9-tetrahydrocannabinol

Various psychiatric disorders such as major depression are associated with abnormalities in emotional processing. Evidence indicating involvement of the endocannabinoid system in emotional processing, and thus potentially in related abnormalities, is increasing. In the present study, we examined the role of the endocannabinoid system in processing of stimuli with a positive and negative emotional content in healthy volunteers. A pharmacological functional magnetic resonance imaging (fMRI) study was conducted with a placebo-controlled, cross-over design, investigating effects of the endocannabinoid agonist ∆9-tetrahydrocannabinol (THC) on brain function related to emotional processing in 11 healthy subjects. Performance and brain activity during matching of stimuli with a negative (‘fearful faces’) or a positive content (‘happy faces’) were assessed after placebo and THC administration. After THC administration, performance accuracy was decreased for stimuli with a negative but not for stimuli with a positive emotional content. Our task activated a network of brain regions including amygdala, orbital frontal gyrus, hippocampus, parietal gyrus, prefrontal cortex, and regions in the occipital cortex. THC interacted with emotional content, as activity in this network was reduced for negative content, while activity for positive content was increased. These results indicate that THC administration reduces the negative bias in emotional processing. This adds human evidence to support the hypothesis that the endocannabinoid system is involved in modulation of emotional processing. Our findings also suggest a possible role for the endocannabinoid system in abnormal emotional processing, and may thus be relevant for psychiatric disorders such as major depression.

Effects of long-term etanercept treatment on anxiety- and depression-like neurobehaviors in rats

Growing evidence indicates that there is a correlation between depression and inflammation. Administration of anti-tumor necrosis factor (TNF) agents for treatment of chronic inflammatory diseases, such as psoriasis, was associated with decreased depressive symptoms and increased quality of life in some clinical studies. The aim of the present study was to investigate the effects of chronic etanercept, a TNF-α inhibitor, on anxiety- and depression-like neurobehaviors in rats.Male rats were treated for 8weeks with either saline or etanercept (0.8mg/kg/week, subcutaneously). The anxiety levels of rats were evaluated using the elevated plus maze, a classical rodent model of anxiety and depression was measured using the force swimming test, a behavioral despair task.The anxiety-like neurobehaviors of the animals were found significantly decreased after the etanercept treatment. Etanercept significantly decreased immobility time in rat model of despair test, seemed to have an antidepressive effect in rats. Compared to saline treatment, long-term etanercept treatment had no effect on the total number and pattern of locomotor activities.Findings of the study supported the hypothesis that TNF-α has a role in the modulation of emotional processes and its inhibition may represent a novel strategy for the treatment of affective disorders.

A biopsychosocial clinical reasoning model for Western acupuncture

Background: The ‘layering method’, a clinical reasoning model for Western acupuncture, is a theoretical framework based on pain and tissue mechanisms. This focus on the mechanics of disability is a limitation of the original model. From a holistic viewpoint, the psychological status of an individual should be considered in clinical reasoning models.Objectives: The first objective was to summarize the original layering model. The second was to determine mechanisms underlying integration of sensations and emotions in the human brain and their effect on the body via output transfer systems of the autonomic, immune, and endocrine systems. The third objective was to determine whether acupuncture can modulate similar regions in the brain and to formulate appropriate clinical reasoning questions.Major findings: Interoceptive sensory stimuli and emotions are integrated in limbic and frontal brain regions to allow emotional responses to feedback from the body and provide the individual with a ‘sense of self’. A strong connection with brainstem nuclei modulating output transfer systems allows emotions to regulate homeostatic balance. Acupuncture may be interpreted as an interoceptive stimulus by the brain. Neuroscience research has shown that acupuncture can modulate neural activity in similar brain regions to those processing emotional responses to sensory inputs.Conclusions: Acupuncture may influence emotional responses and their impact on the neurobiology of the human body. A biopsychosocial clinical reasoning model based on the modulation of emotional processing in the brain is proposed. This suggests that acupuncture may be used as an adjuvant to other therapies in disorders with a biopsychosocial component.

Effects of intra-hippocampal injections of the NK2 receptor antagonist saredutant on the elevated plus maze, and the mouse defense test battery

Intracerebroventricular (i.c.v.) or intraperitoneal (IP) administration of saredutant (SR48968), an NK2 receptor antagonist, produces anxiolytic-like effects in rodents in a number of animal models of anxiety. NK2 binding sites are present in several limbic structures in rats, including the hippocampus, thalamus, septum and prefrontal cortex, suggesting involvement in the modulation of emotional processes. The current study investigated the behavioral effects of saredutant infused into the ventral hippocampus (VH), a structure associated with cognitive and emotional processes, to clarify the neural substrate underlying the anxiolytic-like effect of the compound. Saredutant (10, 100 or 500 pmol/0.2 μL) was injected bilaterally into the VH of male CD-1 mice tested in the elevated plus-maze and mouse defense test battery (MDTB). Results from the EPM showed that microinjections of 10 pmol/0.2 μL of saredutant increased entries and time spent in the open arms and enhanced end-arm exploration. In the MDTB, saredutant (500 pmol/0.2 μL) decreased vocalizations and increased escape attempts in mice confronted with a rat. Taken together, these results suggest that hippocampal tachykinin mechanisms are involved in the modulation of anxiety and defensive behaviors.

Differential modulation of emotion processing by single dose serotonergic and noradrenergic antidepressants – a pharmaco-fMRI study

Differential modulation of emotion processing by single dose serotonergic and noradrenergic antidepressants – a pharmaco-fMRI study

Altered CB1 receptor‐signaling in prefrontal cortex from an animal model of depression is reversed by chronic fluoxetine

Bilateral olfactory bulbectomy in the rat (OBX) induces behavioral, neurochemical, and structural abnormalities similar to those observed in human depression that are normalized after chronic, but not acute, treatment with antidepressants. In our study, OBX animals exhibited significant increases in both CB(1) receptor density ([(3)H]CP55490 binding) and functionality (stimulation of [(35)S]GTPgammaS binding by the cannabinoid (CB) agonist WIN 55212-2) at the prefrontal cortex (PFC). After chronic treatment with fluoxetine (10 mg/kg/day, 14 days, s.c.), OBX-induced hyperactivity in the open-field test was fully abolished. Interestingly, chronic fluoxetine fully reversed the enhanced CB(1)-receptor signaling in PFC observed following OBX. The CB agonist Delta(9)-tetrahydrocannabinol (5 mg/kg, i.p., 1 day) did not produce any behavioral effect in sham-operated animals but returned locomotor activity to control values in OBX rats. As both acute administration of Delta(9)-tetrahydrocannabinol and chronic fluoxetine elicited a similar behavioral effect in the OBX rat, it is not unlikely that the regionally selective enhancement of CB(1) receptor-signaling in the PFC could be related with the altered OBX behavior. Our findings reinforce the utility of this animal model to further investigating the implication of the endocannabinoid system in the modulation of emotional processes and its potential role in the adaptive responses to chronic antidepressants.

Effects of the cannabinoid CB1 receptor antagonist rimonabant in models of emotional reactivity in rodents

The endocannabinoid system has been implicated in the modulation of emotional processes. These experiments aimed to investigate the effects of the cannabinoid CB1 receptor antagonist rimonabant (SR141716) in animal models measuring aspects of emotional reactivity and depression. Rimonabant had weak anxiolytic-like activity in the elevated plus-maze and failed to affect flight and risk assessment activities in the mouse defense test battery (MDTB). It produced clear anxiolytic-like effects in the Vogel conflict test (.3-3 mg/kg intraperitoneal [i.p.]) and on defensive aggression in the MDTB (1 and 10 mg/kg, i.p.). The effects of rimonabant in the MDTB paralleled those observed with CB1 receptor knockout mice in this procedure. In the forced-swimming test in rats and the tonic immobility paradigm in gerbils, rimonabant (3 and 10 mg/kg per os [p.o.]) produced antidepressant-like effects that were comparable to those observed with the reference antidepressant, fluoxetine. In the chronic mild stress model in mice, repeated administration of rimonabant (10 mg/kg, p.o.) for 5 weeks improved the deleterious effects produced by stress. These findings point further to a role for the endocannabinoid system in the modulation of emotional processes and suggest that it may be primarily involved in the adaptive responses to unavoidable stressful stimuli.

Evidence that the lateral septum is involved in the antidepressant-like effects of the vasopressin V1b receptor antagonist, SSR149415.

Previous experiments with the first selective nonpeptide vasopressin V1b receptor antagonist SSR149415 ((2S, 4R)-1-[5-chloro-1-[(2,4-dimethoxyphenyl)sulfonyl]-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimethyl-2-pyrrolidinecarboxamide) have shown that the drug elicits anxiolytic- and antidepressant-like effects following systemic administration. Extrahypothalamic V1b receptors have been suggested to be involved in these effects as evidenced by the findings that hypophysectomized rats were still sensitive to the antistress action of SSR149415. The first objective of the present work aimed at locating V1b receptors in the rat limbic brain using anti-V1b receptor immunohistochemistry. The immunolabeling revealed high densities of V1b receptors in the lateral septum, the amygdala, the bed nucleus of the stria terminalis, the hippocampal formation, and in several cortical areas. Since the lateral septum is well known to participate in the modulation of emotional processes, the second objective of this study went on to evaluate the behavioral effects of an infusion of SSR149415 into the lateral septum and to determine whether its behavioral effects are mediated by this structure. Animals were tested in models classically used for the screening of anxiolytics (ie the punished drinking and elevated plus-maze tests) and antidepressants (ie the forced-swimming test). Bilateral intraseptal infusion of SSR149415 (10 and 100 ng) produced a decrease in immobility time in the forced-swimming test, indicating antidepressant-like effects. In contrast, the behavior of rats in the punished drinking procedure or in the elevated plus-maze test was not modified by intraseptal infusion of SSR149415. These findings suggest that V1b receptors located in the lateral septum participate in the antidepressant- but not the anxiolytic-like action of SSR149415 in rats.

Neuropeptide Y (NPY) and depression: From animal studies to the human condition

Neuropeptide Y (NPY) is widely distributed throughout the central nervous system (CNS) and is one of the most conserved peptides in evolution, suggesting an important role in the regulation of basic physiological functions. In addition, both pre-clinical and clinical evidence have suggested that NPY, together with its receptors, may have a direct implication in several psychiatric disorders, including depression and related illnesses. NPY-like immunoreactivity and NPY receptors are expressed throughout the brain, with varying concentrations being found throughout the limbic system. Such brain structures have been repeatedly implicated in the modulation of emotional processing, as well as in the pathogenesis of depressive disorders. This review will concentrate on the distribution of NPY, its receptors, and the putative role played by this peptide in depressive illness based on both pre-clinical and clinical evidence.

Anxiolytic- and antidepressant-like effects of the non-peptide vasopressin V1b receptor antagonist, SSR149415, suggest an innovative approach for the treatment of stress-related disorders.

The limbic localization of the arginine vasopressin V(1b) receptor has prompted speculation as to a potential role of this receptor in the control of emotional processes. To investigate this possibility, we have studied the behavioral effects of SSR149415, the first selective and orally active non-peptide antagonist of vasopressin V(1b) receptors, in a variety of classical (punished drinking, elevated plus-maze, and light/dark tests) and atypical (fear/anxiety defense test battery and social defeat-induced anxiety) rodent models of anxiety, and in two models of depression [forced swimming and chronic mild stress (CMS)]. When tested in classical tests of anxiety, SSR149415 produced anxiolytic-like activity at doses that ranged from 1 to 30 mg/kg (i.p. or p.o.), but the magnitude of these effects was overall less than that of the benzodiazepine anxiolytic diazepam, which was used as a positive control. In contrast, SSR149415 produced clear-cut anxiolytic-like activity in models involving traumatic stress exposure, such as the social defeat paradigm and the defense test battery (1-30 mg/kg, p.o.). In the forced swimming test, SSR149415 (10-30 mg/kg, p.o.) produced antidepressant-like effects in both normal and hypophysectomized rats. Moreover, in the CMS model in mice, repeated administration of SSR149415 (10 and 30 mg/kg, i.p.) for 39 days improved the degradation of the physical state, anxiety, despair, and the loss of coping behavior produced by stress. These findings point to a role for vasopressin in the modulation of emotional processes via the V(1b) receptor, and suggest that its blockade may represent a novel avenue for the treatment of affective disorders.

Increased anxiety and synaptic plasticity in estrogen receptor beta -deficient mice.

Estrogens are powerful modulators of neuronal physiology and in humans may affect a broad range of functions, including reproductive, emotional, and cognitive behaviors. We studied the contribution of estrogen receptors (ERs) in modulation of emotional processes and analyzed the effects of deleting ERalpha or ERbeta in mice. Behavior consistent with increased anxiety was observed principally in ERbeta mutant females and was associated with a reduced threshold for the induction of synaptic plasticity in the basolateral amygdala. Local increase of 5-hydroxytryptamine 1a receptor expression in medial amygdala may contribute to these changes. Our data show that, particularly in females, there is an important role for ERbeta-mediated estrogen signaling in the processing of emotional behavior.

Behavioral and neurochemical changes following predatory stress in mice

This article had several objectives. First it aimed at investigating the anxiogenic-like behaviors elicited by unavoidable cat exposure and/or cat odor across nine strains of mice (BALB/c, C57BL/6, C3H, CBA, DBA/2, NMRI, NZB, SJL, Swiss) in a modified version of the free-exploration test. The second objective was to investigate possible neurochemical changes following cat exposure in Swiss mice by measuring the turnover of dopamine (DA), noradrenaline (NA) and serotonin (5-HT) in several brain regions known to be involved in the modulation of emotional processes (hippocampus, hypothalamus and striatum). Finally, the third objective was to examine the effects of anxiolytic drug treatments on the anxiogenic responses elicited by a cat odor (i.e. a feces) in Swiss mice previously exposed to a cat using the free-exploration test. Results from the strain comparison showed that mice could be divided into three distinct groups: two non-reactive strains (NZB and SJL) which were relatively insensitive to predatory exposure and/or odor; five intermediate-reactive strains (Swiss, NMRI, CBA, C3H and BALB/c) which displayed clear anxiogenic-like responses only when exposed to both cat and, subsequently, to feces; and two high reactive strains (C57BL/6 and DBA/2) which showed anxiogenic-like reactions following cat exposure, regardless of the stimulus (clay or feces) present in the free-exploration cage. Neurochemical data revealed that, while brain levels of NA, DA, 5-HT in cat exposed Swiss mice were not significantly different from those of control animals, turnover rates of these monoamines were increased in the hippocampus (NA and 5-HT), hypothalamus and striatum (DA) after cat exposure. Results from pharmacological experiments indicated that repeated administration of the 5-HT reuptake inhibitor fluoxetine (5–20 mg/kg, twice a day, for 5 days) completely abolished avoidance of the cat feces in Swiss mice previously exposed to the predator. Neither acute nor repeated administration of the classical anxiolytic diazepam was able to reduce avoidance behavior of the anxiogenic stimulus in the free-exploration test. Taken together, these findings indicate that the exposure of mice to unavoidable predatory stimuli is associated with behavioral and neurochemical changes consistent with increased anxiety.