Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress

Vialou, Vincent; Thibault, Mackenzie; Kaska, Sophia; Cooper, Sarah; Gajewski, Paula A.; Eagle, Andrew L.; Mazei-Robison, Michelle S.; Nestler, Eric J.; Robison, Alfred J.

doi:10.1016/j.neuropharm.2015.07.005

Cited by 67 publications

(74 citation statements)

References 29 publications

(61 reference statements)

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“…We have also demonstrated ΔFosB induction in numerous brains regions in addition to the NAc after chronic fluoxetine administration (Vialou et al, 2014b). A major goal for future research is to carry out studies, analogous to those described above for NAc, to delineate the neural and behavioral phenotype mediated by ΔFosB for each of the brain regions implicated.…”

Section: Induction Of δFosb In Other Brain Regionsmentioning

confidence: 86%

“…Chronic administration of fluoxetine has recently been shown to increase levels of full-length FosB within the NAc 24 hr after the last drug exposure (Vialou et al, 2014b). This is a surprising finding, since full-length FosB is highly unstable and, in chronic stress or chronic drug abuse models, its levels are not elevated beyond 2–4 hr after each exposure.…”

Section: Induction Of δFosb In Nucleus Accumbens By Chronic Antidementioning

confidence: 99%

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∆FosB: A transcriptional regulator of stress and antidepressant responses

Nestler

2015

European Journal of Pharmacology

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ΔFosB is a member of the Fos family of transcription factors. While other family members are induced rapidly but transiently in response to a host of acute stimuli, ΔFosB is unique in that it accumulates in response to repeated stimulation due to its unusual protein stability. Such prolonged induction of ΔFosB, within nucleus accumbens (NAc), a key brain reward region, has been most studied in animal models of drug addiction, with considerable evidence indicating that ΔFosB promotes reward and motivation and serves as a mechanism of drug sensitization and increased drug self-administration. In more recent years, prolonged induction of ΔFosB has also been observed within NAc in response to chronic administration of certain forms of stress. Increasing evidence indicates that this induction represents a positive, homeostatic adaptation to chronic stress, since overexpression of ΔFosB in this brain region promotes resilience to stress, whereas blockade of its activity promotes stress susceptibility. Chronic administration of several antidepressant medications also induces ΔFosB in the NAc, and this induction is required for the therapeutic-like actions of these drugs in mouse models. Validation of these rodent findings is the demonstration that depressed humans, examined at autopsy, display reduced levels of ΔFosB within the NAc. As a transcription factor, ΔFosB produces this behavioral phenotype by regulating the expression of specific target genes, which are under current investigation. These studies of ΔFosB are providing new insight into the molecular basis of depression and antidepressant action, which is defining a host of new targets for possible therapeutic development.

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Section: Induction Of δFosb In Other Brain Regionsmentioning

confidence: 86%

Section: Induction Of δFosb In Nucleus Accumbens By Chronic Antidementioning

confidence: 99%

∆FosB: A transcriptional regulator of stress and antidepressant responses

Nestler

2015

European Journal of Pharmacology

Self Cite

157

131

View full text Add to dashboard Cite

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“…Induction of full-length FosB and ⌬FosB in the dorsal hippocampus has been previously reported with both experimenter-and self-administered cocaine, as well as stress and antidepressants (Perrotti et al, 2008;Vialou et al, 2015). Here, we used 20 mg/kg cocaine intraperitoneal injection to assess induction of FosB and ⌬FosB in dorsal and ventral hippocampus subregions, because this dose is well known to cause robust induction throughout the brain (Perrotti et al, 2008;Robison et al, 2013).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of HippocampalFosbExpression Controls Behavioral Responses to Cocaine

et al. 2019

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Drug addiction results in part from maladaptive learning, including the formation of strong associations between the drug and the circumstances of consumption. However, drug-induced changes in gene expression underlying the saliency of these associations remain understudied. Consolidation of explicit memories occurs within the hippocampus, and we have shown that spatial learning induces expression of the transcription factor ⌬FosB in hippocampus and that this induction is critical for learning. Drugs of abuse also upregulate ⌬FosB in hippocampus, but the mechanism of its induction by cocaine and its role in hippocampus-dependent cocaine responses is unknown. We investigated differences in mouse dorsal and ventral hippocampal ⌬FosB expression in response to chronic cocaine, because these regions appear to regulate distinct cocaine-related behaviors. We found that cocaine-mediated induction of ⌬FosB was subregion-specific, and that ⌬FosB transcriptional activity in both the dorsal and ventral hippocampus is necessary for cocaine conditioned place preference. Further, we characterize changes in histone modifications at the FosB promoter in hippocampus in response to chronic cocaine and found that locus-specific epigenetic modification is essential for FosB induction and multiple hippocampusdependent behaviors, including cocaine place preference. Collectively, these findings suggest that exposure to cocaine induces histone modification at the hippocampal FosB gene promoter to cause ⌬FosB induction critical for cocaine-related learning.

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“…Recent work on human drug addiction has also demonstrated a role of BNST in withdrawal-related anxiety and relapse, indicating an intrinsic link between this stress response region and the reward system. The nucleus accumbens (NAc) is a vital component in the reward circuitry 5–7 , which responds to stress signals 8, 9 and has a dominant effect on anxiety regulation 10 . However, with the exception of one 15-year-old anatomical observation 11 , the connectivity between NAc and BNST, and whether it is necessary in producing anxiety-related behavior, remains unexplored.…”

Section: Introductionmentioning

confidence: 99%

A new GABAergic projection from the BNST onto accumbal parvalbumin neurons controls anxiety

Xiao

Zhou

Wei

et al. 2019

Preprint

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1The prevailing view is that parvalbumin (PV) interneurons play modulatory 2 roles in emotional response through local medium spiny projection neurons 3 (MSNs). Here, we show that PV activity within the nucleus accumbens shell 4 (sNAc) is required for producing anxiety-related avoidance when mice are 5 under anxiogenic situations; sNAc PV neurons exhibited high excitability in 6 chronically stressed mice model, which generated excessive maladaptive 7 avoidance behavior in an anxiogenic context. We also discovered a novel 8 GABAergic projections from the anterior dorsal bed nuclei of stria terminalis 9 (adBNST) to sNAc PV neurons; optogenetic activation of these afferent 10 terminals in sNAc produced an anxiolytic effect via GABA transmission. Next, 11 we further demonstrated that chronic stressors attenuated the inhibitory 12 synaptic transmission at adBNST GABA sNAc PV synapses, which in turn 13 explains the hyperexcitability of sNAc PV neurons on stressed models; therefore, 14 activation of these GABAergic afferents in sNAc rescued the excessive 15 avoidance behavior related to anxious state. 16Our findings reveal the coordination between BNST and NAc through an 17 inhibitory architecture in controlling of anxiety-related response and provide a 18 neurobiological basis for therapeutic interventions in pathological anxiety. 19 Introduction 1 Stressors and stress responses are critical for guiding both approach and 2 avoidance behaviors in animals and humans. Exposure to chronic, 3 unpredictable stressors leads to increased anxiety responses, including 4 excessive avoidance behavior, and this exposure has been adopted to study 5 anxious state-related behaviors 1, 2 . The bed nucleus of the stria terminalis 6 (BNST), a subregion of the extended amygdala, is a critical node in the stress 7 response 3, 4 . Recent work on human drug addiction has also demonstrated a 8 role of BNST in withdrawal-related anxiety and relapse, indicating an intrinsic 9 link between this stress response region and the reward system. The nucleus 10 accumbens (NAc) is a vital component in the reward circuitry 5-7 , which 11 responds to stress signals 8, 9 and has a dominant effect on anxiety regulation 10 . 12 However, with the exception of one 15-year-old anatomical observation 11 , the 13 connectivity between NAc and BNST, and whether it is necessary in producing 14 anxiety-related behavior, remains unexplored. Furthermore, GABAergic 15 efferents originating from the BNST are predominantly sent downstream 12, 13 ; 16 however, the nature and function of any GABAergic input to NAc is unknown.17 Medium spiny neurons that express dopamine 1 and 2 receptors (D1-and 18 D2-MSNs) are the predominant neural population in the NAc . Regarding 19 anxiety regulation, it is accepted that D1-MSNs are not involved in 20 anxiety-related behavior, but play roles in modulating reward-related 21 responses 14, 15 whereas D2-MSNs may regulate anxiety-related aversion or avoidance behavior 16 . However, the role of D2-MSNs are not entirely clear 1 because ot...

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Differential induction of FosB isoforms throughout the brain by fluoxetine and chronic stress

Cited by 67 publications

References 29 publications

∆FosB: A transcriptional regulator of stress and antidepressant responses

∆FosB: A transcriptional regulator of stress and antidepressant responses

Epigenetic Regulation of HippocampalFosbExpression Controls Behavioral Responses to Cocaine

A new GABAergic projection from the BNST onto accumbal parvalbumin neurons controls anxiety

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