Effects of cocaine and withdrawal on the mouse nucleus accumbens transcriptome.

paper Cited Public

Authors: Eipper-Mains, J E; Kiraly, D D; Duff, M O; Horowitz, M J; McManus, C J; Eipper, B A; Graveley, B R; Mains, R E
Year: 2013
Journal: Genes, brain, and behavior
PMID: 23094851
DOI: 10.1111/j.1601-183X.2012.00873.x
PMCID: PMC3553295

Figure 1

High-throughput sequence analysis of NAc mRNA(A-C) Pairwise scatter plots of mRNA expression data for NAc libraries; shown as log10(RPKM) per sample. Ribosomal and mitochondrial genes are not included in the scatter plots. R2 values were calculated by least squares best fit. Abbreviations: Sal, Saline; Coc, Cocaine; W/D, Withdrawal; RPKM, reads per kilobase gene model per million mapped reads (Mortazavi et al., 2008). (D) RPKM data for 47 transcripts in the Saline library are compared to qPCR data (normalized to Glyceraldehyde 3-phosphate dehydrogenase, GAPDH) for the same transcripts; Pearson’s Coefficient represents the linear correlation coefficient, r. (E) Cocaine/Saline ratios for the same 47 transcripts were calculated using RPKM data and qPCR data. Pearson’s Coefficient represents the linear correlation coefficient, r, between two samples, X and Y. Pearson’s r = covariance(X,Y)/σXσY, where σ is the standard deviation.

LLM interpretation

This figure consists of five panels analyzing NAc mRNA expression. Panels A-C are pairwise scatter plots comparing $\log_{10}(\text{RPKM})$ values between Saline vs. Cocaine ($R^2=0.952$), Saline vs. Withdrawal ($R^2=0.946$), and Cocaine vs. Withdrawal ($R^2=0.958$), all showing strong linear correlations. Panel D is a scatter plot comparing $\log_{10}(\text{RPKM})$ to $\log_{10}(\text{qPCR})$ values for 47 transcripts in the Saline group (Pearson's $r=0.75$), and Panel E compares the Cocaine/Saline ratios between the two methods (Pearson's $r=0.60$), with data points color-coded by transcript category (e.g., Glu, GABA, Ach).

Figure 2

Differential regulation of clusters of genes in the NAc following cocaine and withdrawal(A) Normalized mRNA frequency as a function of total reads for NAc lysate libraries (Saline, Cocaine, Withdrawal) was calculated for all genes in which one sample had an RPKM ≥ 1.0 (n = 13,184). Hierarchical gene expression clustering using Gene Cluster 3.0 and Java TreeView generated the dendrogram and heat map. Z-score was computed on normalized mRNA frequency across all samples. Blue, low expression; yellow, high expression; grey, no expression. Gene lists from the indicated Clusters (i-v) were used in subsequent protein class and pathway analyses. (B) The effects of Cocaine on one of the protocadherins identified as a target were verified. Subcellular fractionation of striatal tissue revealed enrichment of PCDH10 at the PSD. PSDs purified from the striata of Saline and Cocaine treated mice were analyzed for PCDH10; after normalization to βIII tubulin, the Coc/Sal ratio for PCDH10 rose 24% (P < 0.01; t-test).

LLM interpretation

Figure A is a hierarchical clustering heat map showing relative mRNA expression (Z-score) across three NAc tissue lysate conditions: Saline (S), Cocaine (C), and Withdrawal (W), with five distinct gene clusters (i-v) exhibiting varying patterns of increase or decrease. Figure B consists of western blots showing the subcellular enrichment of PCDH10 in the PSD fraction and a comparison between Saline and Cocaine treated mice. The bottom blot in B indicates a protein increase for PCDH10 in Cocaine-treated samples relative to Saline, normalized to Tubulin.

Figure 3

Gαi and Gαs heterotrimeric G-protein signaling schematicModel based on Panther Pathway diagram (http://www.pantherdb.org). Venn diagram depicts color key for signaling components. Genes labeled yellow showed a sustained increase in Coc and W/D (cluster i), red genes increased in W/D only (cluster ii), and blue genes had decreased expression in both Coc and W/D (cluster v); overlap colors indicate contribution of > 1 cluster to signaling group. For example, GPCRs, which appear in all three clusters, are shown in magenta. Genes from Clusters i, ii, and v were used for this analysis. Abbreviations: Coc, Cocaine; W/D, Withdrawal.

LLM interpretation

This figure is a schematic diagram illustrating G$\alpha$i and G$\alpha$s heterotrimeric G-protein signaling pathways within a cell, from the membrane to the nucleus. A Venn diagram color key indicates gene expression changes across Cocaine (Coc) and Withdrawal (W/D) conditions: yellow for sustained increase in both, red for increase in W/D only, and blue for sustained decrease in both. The diagram maps these expression patterns onto specific signaling components, including GPCRs, adenylate cyclase, PKA, and the transcription factor CREB.

Figure 4

Regulation of Receptors for Biogenic AminesRPKM data are shown for dopamine, adrenergic and serotonin receptor transcripts (RPKM > 1) in the Saline library. Z-scores were calculated as described in Methods. Transcripts included in this group but expressed at an RPKM < 1 are listed to the side. Ppp1r1b (DARPP32), a multiply phosphorylated phosphatase inhibitor highly expressed in medium spiny neurons, is included for comparison.

LLM interpretation

This figure consists of a heatmap and a corresponding bar chart showing the expression of biogenic amine receptors across three conditions: Saline, Cocaine, and Withdrawal. The heatmap displays relative expression (Z-score) from lower (blue) to higher (yellow), while the bar chart quantifies baseline expression in the Saline group using RPKM. The receptors are categorized into Dopamine, Adrenergic, and Serotonin groups, with *Ppp1r1b* (DARPP32) included as a high-expression comparison.

Figure 5

Regulation of Genes Affecting GABAergic TransmissionData were analyzed as described for Figure 4. The transcripts encoding glutamic acid decarboxylase 65 and 67 (Gad1 and Gad2) are expressed at similar levels. GABA transport into synaptic vesicles requires Slc36a1; retrieval of GABA from extracellular space requires Slc6a1, Slc6a13, or Slca11. Multiple ionotropic GABAA receptor subunits are expressed in the NAc; expression of metabotropic GABAB receptor Gabbr1 greatly exceeds expression of Gabbr2.

LLM interpretation

This figure consists of a heatmap and a corresponding bar chart showing the expression of genes related to GABAergic transmission under three conditions: Saline, Cocaine, and Withdrawal. The heatmap displays relative expression (Z-score) across these conditions, while the bar chart quantifies baseline expression levels in RPKM for the saline group. The genes are categorized into functional groups: Synthesis (*Gad1, Gad2*), Transporters (*Slc36a1, Slc6a1, Slc6a13, Slc6a11*), and $\text{GABA}_{\text{A}}$ and $\text{GABA}_{\text{B}}$ receptors.

Figure 6

Regulation of Genes Affecting Glutamatergic TransmissionData were analyzed as described for Figure 4. Expression of all three vesicular glutamate transporters (Vglut) and four of the plasma membrane glutamate transporters (Slc1a1, Slc1a2, Slc1a3, Slc1a6) was above the cutoff level. Multiple subunits of the ionotropic glutamate receptors (AMPA, NMDA, and Kainate) and multiple metabotropic glutamate receptors are expressed at similar levels.

LLM interpretation

This figure consists of a heatmap and a corresponding bar chart showing the expression of genes related to glutamatergic transmission across three conditions: Saline, Cocaine, and Withdrawal. The heatmap displays relative expression (Z-score) for various transporters and glutamate receptors (AMPA, NMDA, Kainate, and Metabotropic), while the bar chart quantifies the expression levels in the saline group using RPKM. Key observations include high saline expression for *Slc1a2* and *Grin1*, and varying expression patterns across the drug conditions for the listed gene subunits.

Figure 7

Regulation of Genes Affecting Cholinergic TransmissionData were analyzed as described for Figure 4. Although only a small percentage of the neurons in the NAc are cholinergic, choline acetyltransferase (ChAT), high affinity plasma membrane choline transporter (Slc5a7) and vesicular acetylcholine transporter (Slc18a3) transcript levels all fall above the 1 RPKM cutoff. Only three of the many nicotinic acetylcholine receptor subunits are expressed in the NAc while all five muscarinic receptors are expressed. Expression of each of the genes involved in cholinergic transmission is elevated in withdrawal.

LLM interpretation

This figure consists of a heatmap and a corresponding bar chart showing the expression of genes related to cholinergic transmission in the NAc across three conditions: Saline, Cocaine, and Withdrawal. The heatmap displays relative expression (Z-score) from lower (blue) to higher (yellow), indicating that expression of the listed genes is elevated during withdrawal. The bar chart quantifies the baseline expression levels in RPKM for the saline group, while a side list identifies genes with RPKM < 1.

Figure 8

Regulation of Genes Affecting Endocannabinoid SignalingRPKM data were analyzed as described for Figure 4. While transcripts encoding the two enzymes that synthesize the endocannabinoid 2-arachidonoylglycerol (diacylglycerol lipase α and β; Dagla and Daglb) are expressed at similar levels in the NAc, they respond to cocaine in an opposite manner. Expression of transcripts encoding cannabinoid receptor 1 (Cnr1) greatly exceeds that of cannabinoid receptor 2 (Cnr2) and is responsive to cocaine.

LLM interpretation

This figure consists of a heatmap and a corresponding bar chart showing the expression of genes related to endocannabinoid signaling across three conditions: Saline, Cocaine, and Withdrawal. The heatmap displays relative expression (Z-score) for genes including *Dagla*, *Daglb*, *Napepld*, *Mgll*, *Faah*, and *Cnr1*, while the bar chart quantifies baseline expression in RPKM for the saline group. *Cnr2* is noted separately as having an RPKM < 1.

#	Section	Preview
20	Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways	Dopamine, norepinephrine, and serotonin receptors expressed in the NAc play a critical role in…
21	Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways	Over 90% of the neurons in the NAc are GABAergic medium spiny interneurons (Kemp and Powell, 1971);…
22	Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways	Glutamatergic signaling plays an essential role in drug abuse, with major glutamatergic inputs onto…
23	Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways	showed a sustained increase while expression of Grik4 and Grik5 showed a sustained decrease.…
24	Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways	A small population of giant aspiny cholinergic interneurons is found in the NAc (Threlfell and…
25	Results — Widespread effects of cocaine and withdrawal on catecholaminergic, GABAergic, cholinergic, glutamatergic, and endocannabinoid pathways	The endocannabinoid system is heavily involved in many reward-seeking responses to drugs of abuse…
26	Discussion	Single-gene, proteomic, and microarray analyses demonstrated that cocaine produces widespread,…
27	Discussion — Global comparisons of gene expression identify signaling pathways targeted by cocaine — Cadherin/Wnt pathways	By sequencing PSD-localized, cocaine-regulated striatal microRNAs, we previously identified miR-8…
28	Discussion — Global comparisons of gene expression identify signaling pathways targeted by cocaine — Cadherin/Wnt pathways	A few studies have suggested a role for cell adhesion and extracellular matrix proteins in the…
29	Discussion — Global comparisons of gene expression identify signaling pathways targeted by cocaine — Heterotrimeric G-protein pathways	Transcripts encoding GPCRs, heterotrimeric G-protein subunits, regulators of G-protein signaling…
30	Discussion — Global comparisons of gene expression identify signaling pathways targeted by cocaine — Heterotrimeric G-protein pathways	Consistent with a major role for cadherins in the response to cocaine, seven transmembrane cadherins…
31	Discussion — Neurotransmitter-specific effects	Expression of the D3 dopamine receptor (Drd3) increased in response to Cocaine and remained elevated…
32	Discussion — Neurotransmitter-specific effects	Expression of many of the genes responsible for GABA synthesis, transport into synaptic vesicles,…
33	Discussion — Neurotransmitter-specific effects	A growing body of literature has focused on the role of AMPA, NMDA and kainate receptor-mediated…
34	Discussion — Neurotransmitter-specific effects	Cholinergic transmission in the NAc contributes to addiction through the modulation of dopamine…
35	Conclusion	We used next-generation sequencing to generate a comprehensive catalog of transcriptional changes…

Citation	PMID	DOI	Status
Adamczyk, P et al., Brain Res, Long-lasting increase in [(3)H]CP55,940 binding to CB1 receptors following cocaine self-administration and its withdrawal in rats	22425184	10.1016/j.brainres.2012.02.052	Cited
Adamczyk, P et al., Brain Res, The effects of cannabinoid CB1, CB2 and vanilloid TRPV1 receptor antagonists on cocaine addictive behavior in rats	22325096	10.1016/j.brainres.2012.01.030	Cited
Beenhakker, MP et al., J Neurosci, 2010, Astrocytes as gatekeepers of GABAB receptor function	21068331	10.1523/JNEUROSCI.3243-10.2010	Cited
Bolteus, AJ et al., J Neurosci, 2004, GABA release and uptake regulate neuronal precursor migration in the postnatal subventricular zone	15342728	10.1523/JNEUROSCI.1999-04.2004	Cited
Boudreau, AC et al., J Neurosci, 2007, Cell surface AMPA receptors in the rat nucleus accumbens increase during cocaine withdrawal but internalize after cocaine challenge in association with altered activation of mitogen-activated protein kinases	17898233	10.1523/JNEUROSCI.2163-07.2007	Cited
Brebner, K et al., Alcohol Alcohol, 2002, A potential role for GABA(B) agonists in the treatment of psychostimulant addiction	12217943	10.1093/alcalc/37.5.478	Cited
Brooks, AN et al., Genome Res, 2011, Conservation of an RNA regulatory map between Drosophila and mammals	20921232	10.1101/gr.108662.110	Cited
Conrad, KL et al., Neuroscience, 2010, Dopamine receptor expression and distribution dynamically change in the rat nucleus accumbens after withdrawal from cocaine self-administration	20435100	10.1016/j.neuroscience.2010.04.056	Cited
Di Chiara, G et al., J Pharmacol Exp Ther, 1988, Opposite effects of mu and kappa opiate agonists on dopamine release in the nucleus accumbens and in the dorsal caudate of freely moving rats	2855239	—	Cited
Dreyer, J-L, Genome Med, 2010, New insights into the roles of microRNAs in drug addiction and neuroplasticity	21205279	10.1186/gm213	Cited
Eipper-Mains, JE et al., Front Genet, 2012, Global Approaches to the Role of miRNAs in Drug-Induced Changes in Gene Expression	22707957	10.3389/fgene.2012.00109	Cited
Eipper-Mains, JE et al., RNA, 2011, microRNA-Seq reveals cocaine-regulated expression of striatal microRNAs	21708909	10.1261/rna.2775511	Cited
El Mestikawy, S et al., Nat Rev Neurosci, 2011, From glutamate co-release to vesicular synergy: vesicular glutamate transporters	21415847	10.1038/nrn2969	Cited
Erhardt, S et al., Naunyn Schmiedebergs Arch Pharmacol, 2002, GABA(B) receptor-mediated modulation of the firing pattern of ventral tegmental area dopamine neurons in vivo	11882912	10.1007/s00210-001-0519-5	Cited
Force, T et al., Sci STKE, 2007, Molecular scaffolds regulate bidirectional crosstalk between Wnt and classical seven-transmembrane-domain receptor signaling pathways	17666710	10.1126/stke.3972007pe41	Cited
Heilig, M et al., Nat Rev Neurosci, 2011, Pharmacogenetic approaches to the treatment of alcohol addiction	22011682	10.1038/nrn3110	Cited
Hoffmann, HM et al., Addict Biol, 2012, Chronic cocaine self-administration modulates ERK1/2 and CREB responses to dopamine receptor agonists in striatal slices	21812869	10.1111/j.1369-1600.2011.00353.x	Cited
Huang, YH et al., Neuron, 2009, In vivo cocaine experience generates silent synapses	19607791	10.1016/j.neuron.2009.06.007	Cited
Hyman, SE et al., Annu Rev Neurosci, 2006, Neural mechanisms of addiction: the role of reward-related learning and memory	16776597	10.1146/annurev.neuro.29.051605.113009	Cited
Kalivas, PW et al., Mol Psychiatry, 2011, New medications for drug addiction hiding in glutamatergic neuroplasticity	21519339	10.1038/mp.2011.46	Cited
Kalivas, PW et al., Neuropharmacology, 2009, Glutamate transmission in addiction	18675832	10.1016/j.neuropharm.2008.07.011	Cited
Kalivas, PW, Nat Rev Neurosci, 2009, The glutamate homeostasis hypothesis of addiction	19571793	10.1038/nrn2515	Cited
Kauer, JA et al., Nat Rev Neurosci, 2007, Synaptic plasticity and addiction	17948030	10.1038/nrn2234	Cited
Kemp, JM et al., Philos Trans R Soc Lond B Biol Sci, 1971, The structure of the caudate nucleus of the cat: light and electron microscopy	4107495	10.1098/rstb.1971.0102	Cited
Kiraly, DD et al., Biol Psychiatry, 2010, Behavioral and morphological responses to cocaine require kalirin7	20452575	10.1016/j.biopsych.2010.03.024	Cited
Kovacs, JJ et al., Dev Cell, 2009, Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways	19853559	10.1016/j.devcel.2009.09.011	Cited
Langmead, B et al., Genome Biol, 2009, Ultrafast and memory-efficient alignment of short DNA sequences to the human genome	19261174	10.1186/gb-2009-10-3-r25	Cited
Le Merrer, J et al., Physiol Rev, 2009, Reward processing by the opioid system in the brain	19789384	10.1152/physrev.00005.2009	Cited
Lee, M-C et al., Neuron, 2010, Metaplasticity at single glutamatergic synapses	20620872	10.1016/j.neuron.2010.05.015	Cited
Lehrmann, E et al., Pharmacogenomics J, 2003, Transcriptional profiling in the human prefrontal cortex: evidence for two activational states associated with cocaine abuse	12629581	10.1038/sj.tpj.6500146	Cited
Liu, Q-s et al., Nature, 2005, Repeated cocaine exposure in vivo facilitates LTP induction in midbrain dopamine neurons	16222299	10.1038/nature04050	Cited
Lull, ME et al., Ann N Y Acad Sci, 2008, Correlating human and animal studies of cocaine abuse and gene expression	18991951	10.1196/annals.1441.013	Cited
Mark, GP et al., Physiol Behav, 2011, Cholinergic modulation of mesolimbic dopamine function and reward	21549724	10.1016/j.physbeh.2011.04.052	Cited
Mash, DC et al., Ann N Y Acad Sci, 1999, D3 dopamine and kappa opioid receptor alterations in human brain of cocaine-overdose victims	10415668	10.1111/j.1749-6632.1999.tb09286.x	Cited
Mash, DC et al., PLoS One, 2007, Gene expression in human hippocampus from cocaine abusers identifies genes which regulate extracellular matrix remodeling	18000554	10.1371/journal.pone.0001187	Cited
McClung, CA et al., Neuropsychopharmacology, 2008, Neuroplasticity mediated by altered gene expression	17728700	10.1038/sj.npp.1301544	Cited
Metzker, ML, Nat Rev Genet, 2010, Sequencing technologies - the next generation	19997069	10.1038/nrg2626	Cited
Morishita, H et al., Curr Opin Cell Biol, 2007, Protocadherin family: diversity, structure, and function	17936607	10.1016/j.ceb.2007.09.006	Cited
Mortazavi, A et al., Nat Methods, 2008, Mapping and quantifying mammalian transcriptomes by RNA-Seq	18516045	10.1038/nmeth.1226	Cited
Nestler, EJ, Nat Neurosci, Is there a common molecular pathway for addiction?	16251986	10.1038/nn1578	Cited
Nestler, EJ, Sci Pract Perspect, The neurobiology of cocaine addiction	18552739	10.1151/spp05314	Cited
Novikova, SI et al., Synapse, 2005, Neuropathology of the cerebral cortex observed in a range of animal models of prenatal cocaine exposure may reflect alterations in genes involved in the Wnt and cadherin systems	15729737	10.1002/syn.20134	Cited
Orio, L et al., J Neurosci, 2009, A role for the endocannabinoid system in the increased motivation for cocaine in extended-access conditions	19369553	10.1523/JNEUROSCI.0563-09.2009	Cited
Pascoli, V et al., Biol Psychiatry, 2011, Cyclic adenosine monophosphate-independent tyrosine phosphorylation of NR2B mediates cocaine-induced extracellular signal-regulated kinase activation	21055728	10.1016/j.biopsych.2010.08.031	Cited
Pierce, RC et al., J Neurosci, 1996, Repeated cocaine augments excitatory amino acid transmission in the nucleus accumbens only in rats having developed behavioral sensitization	8778304	10.1523/JNEUROSCI.16-04-01550.1996	Cited
Ren, Z et al., Neuroscience, 2010, Dopamine D1 and N-methyl-D-aspartate receptors and extracellular signal-regulated kinase mediate neuronal morphological changes induced by repeated cocaine administration	20346392	10.1016/j.neuroscience.2010.03.034	Cited
Saunders, BT et al., Neuropsychopharmacology, 2011, Individual variation in the motivational properties of cocaine	21471956	10.1038/npp.2011.48	Cited
Schousboe, A et al., Biochem Pharmacol, 2004, GABA transporters as drug targets for modulation of GABAergic activity	15451399	10.1016/j.bcp.2004.06.041	Cited
Schousboe, A et al., Future Med Chem, 2011, GABA transport inhibitors and seizure protection: the past and future	21428813	10.4155/fmc.10.288	Cited
Threlfell, S et al., Front Syst Neurosci, 2011, Dopamine signaling in dorsal versus ventral striatum: the dynamic role of cholinergic interneurons	21427783	10.3389/fnsys.2011.00011	Cited
Trapnell, C et al., Nat Biotechnol, 2010, Transcript assembly and quantification by RNA-Seq reveals unannotated transcripts and isoform switching during cell differentiation	20436464	10.1038/nbt.1621	Cited
Tzingounis, AV et al., Nat Rev Neurosci, 2007, Glutamate transporters: confining runaway excitation by shaping synaptic transmission	17987031	10.1038/nrn2274	Cited
Uemura, M et al., Nat Neurosci, 2007, OL-Protocadherin is essential for growth of striatal axons and thalamocortical projections	17721516	10.1038/nn1960	Cited
Wahlstedt, H et al., Genome Res, 2009, Large-scale mRNA sequencing determines global regulation of RNA editing during brain development	19420382	10.1101/gr.089409.108	Cited
Wang, W-X et al., Biochim Biophys Acta, Focus on RNA isolation: obtaining RNA for microRNA (miRNA) expression profiling analyses of neural tissue	18316046	10.1016/j.bbagrm.2008.01.005	Cited
Wang, X et al., PLoS One, Transcriptome-wide identification of novel imprinted genes in neonatal mouse brain	19052635	10.1371/journal.pone.0003839	Cited
Wang, Z et al., Nat Rev Genet, 2009, RNA-Seq: a revolutionary tool for transcriptomics	19015660	10.1038/nrg2484	Cited
Wee, S et al., Psychopharmacology (Berl), 2010, The role of the dynorphin-kappa opioid system in the reinforcing effects of drugs of abuse	20352414	10.1007/s00213-010-1825-8	Cited
Wolf, ME et al., Neurosci Biobehav Rev, 2010, AMPA receptor plasticity in the nucleus accumbens after repeated exposure to cocaine	20109488	10.1016/j.neubiorev.2010.01.013	Cited
Wolf, ME, Trends Neurosci, 2010, The Bermuda Triangle of cocaine-induced neuroadaptations	20655604	10.1016/j.tins.2010.06.003	Cited

In this knowledge base

Title	Year	PMID
Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders.	2021	31477794
A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.	2017	27067016

External

Title	Authors	Journal	Year	Link
Biased Signaling Agonists of Dopamine D3 Receptor Differentially Regulate the Effects of Cocaine On Dopamine Transporter Function.	Cohen SR et al.	—	2025	→
Cocaine-induced gene regulation in D1 and D2 neuronal ensembles of the nucleus accumbens.	Mews P et al.	—	2025	→
Cocaine perturbs neurodevelopment and increases neuroinflammation in a prenatal cerebral organoid model.	Davis JL et al.	—	2025	→
Transcriptional characterization of cocaine withdrawal versus extinction within nucleus accumbens in male rats.	Martínez-Rivera FJ et al.	—	2025	→
Cocaine-Induced Gene Regulation in D1 and D2 Neuronal Ensembles of the Nucleus Accumbens Revealed by Single-Cell RNA Sequencing	Mews P et al.	—	2024	—
Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens.	Mews P et al.	—	2024	→
Exploring the progression of drug dependence in a methamphetamine self-administration rat model through targeted and non-targeted metabolomics analyses.	Song SH et al.	—	2024	→
Abstinence from Escalation of Cocaine Intake Changes the microRNA Landscape in the Cortico-Accumbal Pathway.	Kumaresan V et al.	—	2023	→
Effect of germ-free status on transcriptional profiles in the nucleus accumbens and transcriptomic response to chronic morphine.	Sens JP et al.	—	2023	→
Cocaine-induced projection-specific and cell type-specific adaptations in the nucleus accumbens.	Zinsmaier AK et al.	—	2022	→
Human Pluripotent Stem Cell-Derived Medium Spiny Neuron-like Cells Exhibit Gene Desensitization.	Tam RW et al.	—	2022	→
Molecular genetics of cocaine use disorders in humans.	Fernàndez-Castillo N et al.	—	2022	→
Allele-specific expression and high-throughput reporter assay reveal functional genetic variants associated with alcohol use disorders.	Rao X et al.	—	2021	→
A role for the endocannabinoid enzymes monoacylglycerol and diacylglycerol lipases in cue-induced cocaine craving following prolonged abstinence.	Mitra S et al.	—	2021	→
Cell-type specific knockout of peptidylglycine α-amidating monooxygenase reveals specific behavioral roles in excitatory forebrain neurons and cardiomyocytes.	Powers KG et al.	—	2021	→
Cocaine self-administration induces sex-dependent protein expression in the nucleus accumbens.	López AJ et al.	—	2021	→
Egr2 induction in spiny projection neurons of the ventrolateral striatum contributes to cocaine place preference in mice.	Mukherjee D et al.	—	2021	→
Hippocampal mu opioid receptors are modulated following cocaine self-administration in rat.	De Sa Nogueira D et al.	—	2021	→
Partial connectomes of labeled dopaminergic circuits reveal non-synaptic communication and axonal remodeling after exposure to cocaine.	Wildenberg G et al.	—	2021	→
Reduced cue-induced reinstatement of cocaine-seeking behavior in Plcb1 +/- mice.	Cabana-Domínguez J et al.	—	2021	→
Convergent functional genomics of cocaine misuse in humans and animal models.	Forero DA et al.	—	2020	→
Inherent Motor Impulsivity Associates with Specific Gene Targets in the Rat Medial Prefrontal Cortex.	Sholler DJ et al.	—	2020	→
Prospects for finding the mechanisms of sex differences in addiction with human and model organism genetic analysis.	Datta U et al.	—	2020	→
A pH-sensitive luminal His-cluster promotes interaction of PAM with V-ATPase along the secretory and endocytic pathways of peptidergic cells.	Rao VK et al.	—	2019	→
Cell-Type-Specific Regulation of Nucleus Accumbens Synaptic Plasticity and Cocaine Reward Sensitivity by the Circadian Protein, NPAS2.	Parekh PK et al.	—	2019	→
Neurogenetic determinants and mechanisms of addiction to nicotine and smoked tobacco.	Sharp BM et al.	—	2019	→
Selective allosteric modulation of muscarinic acetylcholine receptors for the treatment of schizophrenia and substance use disorders.	Teal LB et al.	—	2019	→
Sex-Specific Gene Expression in the Mouse Nucleus Accumbens Before and After Cocaine Exposure.	LaRese TP et al.	—	2019	→
Changes in Corticotrope Gene Expression Upon Increased Expression of Peptidylglycine α-Amidating Monooxygenase.	Mains RE et al.	—	2018	→
Estrogen-Dependent Upregulation of <i>Adcyap1r1</i> Expression in Nucleus Accumbens Is Associated With Genetic Predisposition of Sex-Specific QTL for Alcohol Consumption on Rat Chromosome 4.	Spence JP et al.	—	2018	→
A protocadherin gene cluster regulatory variant is associated with nicotine withdrawal and the urge to smoke.	Jensen KP et al.	—	2017	→
Association of the PLCB1 gene with drug dependence.	Cabana-Domínguez J et al.	—	2017	→
Dynamic Expression Changes in the Transcriptome of the Prefrontal Cortex after Repeated Exposure to Cocaine in Mice.	Li M et al.	—	2017	→
Epigenetic dysregulation of protocadherins in human disease.	El Hajj N et al.	—	2017	→
Sigma 2 Receptor/Tmem97 Agonists Produce Long Lasting Antineuropathic Pain Effects in Mice.	Sahn JJ et al.	—	2017	→
Transcriptomic profiling of the ventral tegmental area and nucleus accumbens in rhesus macaques following long-term cocaine self-administration.	Vallender EJ et al.	—	2017	→
Using Kalirin conditional knockout mice to distinguish its role in dopamine receptor mediated behaviors.	LaRese TP et al.	—	2017	→
Post-cocaine changes in regulator of G-protein signaling (RGS) proteins in the dorsal striatum: Relevance for cocaine-seeking and protein kinase C-mediated phosphorylation.	Bilodeau J et al.	—	2016	→
Regulation of nucleus accumbens transcript levels in mice by early-life social stress and cocaine.	Lo Iacono L et al.	—	2016	→
Biomarkers for the development of new medications for cocaine dependence.	Bough KJ et al.	—	2014	→
Constitutive knockout of kalirin-7 leads to increased rates of cocaine self-administration.	Kiraly DD et al.	—	2013	→