Cell Type–Specific Whole-Genome Landscape of ΔFOSB Binding in the Nucleus Accumbens After Chronic Cocaine Exposure

Yeh, Szu-Ying; Estill, Molly; Lardner, Casey K.; Browne, Caleb J.; Minier-Toribio, Angélica; Futamura, Rita; Beach, Katherine F.; McManus, Catherine A.; Xu, Song-Jun; Zhang, Shuo; Heller, Elizabeth A.; Шен, Ли; Nestler, Eric J.

doi:10.1016/j.biopsych.2022.12.021

Cited by 22 publications

(18 citation statements)

References 56 publications

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“…This study is the first to explore the effects of cocaine on D1R-MSN versus D2R-MSN excitability of the NAcSh across sexes, with attention to the effects of estrous cycle before and after drug treatment. We have replicated previous findings that cocaine exposure leads to neuroadaptive effects in the NAcSh of male mice, primarily driven by an effect at D1R-MSN ( 8 , 9 , 10 , 11 , 13 , 39 , 40 , 41 , 42 ). This cocaine-induced D1R-MSN–driven plasticity is thought to be the primary contributor to the rewarding effects of the drug ( 43 ) as well as the locomotor response ( 13 ).…”

Section: Discussionsupporting

confidence: 87%

Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell

Chapp,

Nwakama,

Jagtap

et al. 2024

Biological Psychiatry Global Open Science

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Section: Discussionsupporting

confidence: 87%

Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell

Chapp,

Nwakama,

Jagtap

et al. 2024

Biological Psychiatry Global Open Science

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“…In conclusion, the 5-HT 4 R is over-expressed in the putamen both after DA depletion and DA dyskinesiogenic supplementation. This suggests that two distinct mechanisms are involved: firstly, a post-injury compensatory mechanism, and secondly, a LID-driven maladaptive plasticity mechanism involving FosB/ Δ FosB, which may in turn regulate the transcription of 5-HT 4 R. Indeed, Δ FosB likely binds to the 5-HT 4 R [ 37 ]. Although we do not know, at this stage, whether 5-HT 4 R is involved in motor disorders or is due to compensatory mechanisms, this work raises the broader question of the role of the 5-HT 4 R in the pathophysiology of PD, with possible implications on the pathophysiology of cognitive deficits or mood disorders to which this receptor has been linked in other pathologies.…”

Section: Discussionmentioning

confidence: 99%

Striatal Serotonin 4 Receptor is Increased in Experimental Parkinsonism and Dyskinesia

Cirillo,

Duperrier,

Parekh

et al. 2024

JPD

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Alterations of serotonin type 4 receptor levels are linked to mood disorders and cognitive deficits in several conditions. However, few studies have investigated 5-HT4R alterations in movement disorders. We wondered whether striatal 5-HT4R expression is altered in experimental parkinsonism. We used a brain bank tissue from a rat and a macaque model of Parkinson’s disease (PD). We then investigated its in vivo PET imaging regulation in a cohort of macaques. Dopaminergic depletion increases striatal 5-HT4R in the two models, further augmented after dyskinesia-inducing L-Dopa. Pending confirmation in PD patients, the 5-HT4R might offer a therapeutic target for dampening PD’s symptoms.

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“…For library preparations, we used SMARTer Stranded Total RNA-seq kit v3 - Pico Input Mammalian (Takara Bio, CA). All libraries were in-house tested for quality control (averaging 23 ng/µL, Qbid; range peak size 300-500 bp, Bioanalyzer) 24,25 .…”

Section: Methodsmentioning

confidence: 99%

Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

Martínez-Rivera,

Holt,

Minier-Toribio

et al. 2024

Preprint

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Substance use disorder is characterized by a maladaptive imbalance wherein drug seeking persists despite negative consequences or drug unavailability. This imbalance correlates with neurobiological alterations some of which are amplified during forced abstinence, thereby compromising the capacity of extinction-based approaches to prevent relapse. Cocaine use disorder (CUD) exemplifies this phenomenon in which neurobiological modifications hijack brain reward regions such as the nucleus accumbens (NAc) to manifest craving and withdrawal-like symptoms. While increasing evidence links transcriptional changes in the NAc to specific phases of addiction, genome-wide changes in gene expression during withdrawal vs. extinction (WD/Ext) have not been examined in a context- and NAc-subregion-specific manner. Here, we used cocaine self-administration (SA) in rats combined with RNA-sequencing (RNA-seq) of NAc subregions (core and shell) to transcriptionally profile the impact of experiencing withdrawal in the home cage or in the previous drug context or experiencing extinction training. As expected, home-cage withdrawal maintained drug seeking in the previous drug context, whereas extinction training reduced it. By contrast, withdrawal involving repetitive exposure to the previous drug context increased drug-seeking behavior. Bioinformatic analyses of RNA-seq data revealed gene expression patterns, networks, motifs, and biological functions specific to these behavioral conditions and NAc subregions. Comparing transcriptomic analysis of the NAc of patients with CUD highlighted conserved gene signatures, especially with rats that were repetitively exposed to the previous drug context. Collectively, these behavioral and transcriptional correlates of several withdrawal-extinction settings reveal fundamental and translational information about potential molecular mechanisms to attenuate drug-associated memories.

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Cell Type–Specific Whole-Genome Landscape of ΔFOSB Binding in the Nucleus Accumbens After Chronic Cocaine Exposure

Cited by 22 publications

References 56 publications

Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell

Fundamental Sex Differences in Cocaine-Induced Plasticity of Dopamine D1 Receptor– and D2 Receptor–Expressing Medium Spiny Neurons in the Mouse Nucleus Accumbens Shell

Striatal Serotonin 4 Receptor is Increased in Experimental Parkinsonism and Dyskinesia

Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens

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