Browse
Submit Data
Databases
API
Help

Dataset Information

25 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional signatures in prefrontal cortex confer vulnerability versus resilience to food and cocaine addiction-like behavior.

ABSTRACT: Addiction is a chronic relapsing brain disease characterized by compulsive reward-seeking despite harmful consequences. The mechanisms underlying addiction are orchestrated by transcriptional reprogramming in the reward system of vulnerable subjects. This study aims at revealing gene expression alterations across different types of addiction. We analyzed publicly available transcriptome datasets of the prefrontal cortex (PFC) from a palatable food and a cocaine addiction study. We found 56 common genes upregulated in the PFC of addicted mice in these two studies, whereas most of the differentially expressed genes were exclusively linked to either palatable food or cocaine addiction. Gene ontology analysis of shared genes revealed that these genes contribute to learning and memory, dopaminergic synaptic transmission, and histone phosphorylation. Network analysis of shared genes revealed a protein-protein interaction node among the G protein-coupled receptors (Drd2, Drd1, Adora2a, Gpr6, Gpr88) and downstream targets of the cAMP signaling pathway (Ppp1rb1, Rgs9, Pde10a) as a core network in addiction. Upon extending the analysis to a cell-type specific level, some of these common molecular players were selectively expressed in excitatory neurons, oligodendrocytes, and endothelial cells. Overall, computational analysis of publicly available whole transcriptome datasets provides new insights into the molecular basis of addiction-like behaviors in PFC.

SUBMITTER: Navandar M

PROVIDER: S-EPMC8079697 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Altered functional connectivity of the insular cortex across prefrontal networks in cocaine addiction.

Project description:Interoception is theorized to be an important process mediating substance use disorders, and the insular cortex is recognized as a core neural region supporting interoception. The purpose of this study was to compare the integration of the insular cortex into prefrontal-related resting-state networks between individuals with cocaine dependence and healthy controls. Participants comprised 41 patients with cocaine dependence and 19 controls who underwent a resting-state 3-T functional magnetic resonance imaging scan. Individuals with cocaine dependence demonstrated altered functional connectivity of the insular cortex, predominantly the right insular cortex, with all eight prefrontal-related resting-state networks identified through Independent Component Analysis (ICA). A conjunction analysis demonstrated that the right insular cortex was the neural region with the highest number of common group differences across the networks. There was no evidence that insular cortex connectivity commonly differed between groups for non-prefrontal-related networks. Further, seed-based functional connectivity analyses extended the network analyses and indicated that cocaine dependence was associated with greater connectivity of the right insula with the dorsomedial prefrontal cortex, inferior frontal gyrus, and bilateral dorsolateral prefrontal cortex. These data support the hypothesis that cocaine dependence is related to altered functional interactions of the insular cortex with prefrontal networks. The results suggest possible neural mechanisms by which the insular cortex and interoceptive information influence cognitive control and decision-making processes presumably mediated by prefrontal networks in the cocaine dependence process.

| S-EPMC3708551 | biostudies-literature

A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to food addiction.

Project description:Food addiction is linked to obesity and eating disorders and is characterized by a loss of behavioral control and compulsive food intake. Here, using a food addiction mouse model, we report that the lack of cannabinoid type-1 receptor in dorsal telencephalic glutamatergic neurons prevents the development of food addiction-like behavior, which is associated with enhanced synaptic excitatory transmission in the medial prefrontal cortex (mPFC) and in the nucleus accumbens (NAc). In contrast, chemogenetic inhibition of neuronal activity in the mPFC-NAc pathway induces compulsive food seeking. Transcriptomic analysis and genetic manipulation identified that increased dopamine D2 receptor expression in the mPFC-NAc pathway promotes the addiction-like phenotype. Our study unravels a new neurobiological mechanism underlying resilience and vulnerability to the development of food addiction, which could pave the way towards novel and efficient interventions for this disorder.

| S-EPMC7005839 | biostudies-literature

A specific prelimbic-nucleus accumbens pathway controls resilience versus vulnerability to develop food addiction.

Project description:The aim of this study was to analyse the whole transcriptome profile of medial prefrontal cortex of food addicted and non-addicted Glu-CB1-WT and Glu-CB1-KO mice using total RNA-seq.

2020-02-18 | GSE139482 | GEO

Loss of environmental enrichment increases vulnerability to cocaine addiction.

Project description:Life experiences, especially during critical periods of maturation, such as adolescence, can dramatically affect vulnerability to diseases at adulthood. Early exposure to positive environmental conditions such as environmental enrichment (EE) has been shown to reduce the occurrence and the intensity of neurological and psychiatric disorders including drug addiction. However, whether or not exposure to EE during early stages of life would protect from addiction when, at adulthood, individuals may find themselves in non-enriched conditions has not been investigated. Here we show that switching mice from EE to non-enriched standard environments not only results in the loss of the preventive effects of EE but also increases the rewarding effects of cocaine. This enhanced vulnerability is associated with emotional distress and with increased levels in the mRNA levels of corticotropin releasing factor (CRF) in the bed nucleus of the stria terminalis (BNST), as well as with increases in CREB phosphorylation in the BNST and in the shell of the nucleus accumbens. The increased sensitivity to the rewarding effects of cocaine is completely blocked by the CRF antagonist antalarmin, confirming a major role of the CRF system in the negative consequences of this environmental switch. These results indicate that positive life conditions during early stages of life, if they are not maintained at adulthood, may have negative emotional consequences and increase the risks to develop drug addiction.

| S-EPMC3358749 | biostudies-literature

Subthalamic low-frequency oscillations predict vulnerability to cocaine addiction.

Project description:Identifying vulnerable individuals before they transition to a compulsive pattern of drug seeking and taking is a key challenge in addiction to develop efficient prevention strategies. Oscillatory activity within the subthalamic nucleus (STN) has been associated with compulsive-related disorders. To study compulsive cocaine-seeking behavior, a core component of drug addiction, we have used a rat model in which cocaine seeking despite a foot-shock contingency only emerges in some vulnerable individuals having escalated their cocaine intake. We show that abnormal oscillatory activity within the alpha/theta and low-beta bands during the escalation of cocaine intake phase predicts the subsequent emergence of compulsive-like seeking behavior. In fact, mimicking STN pathological activity in noncompulsive rats during cocaine escalation turns them into compulsive ones. We also find that 30 Hz, but not 130 Hz, STN deep brain stimulation (DBS) reduces pathological cocaine seeking in compulsive individuals. Our results identify an early electrical signature of future compulsive-like cocaine-seeking behavior and further advocates the use of frequency-dependent STN DBS for the treatment of addiction.

| S-EPMC8040637 | biostudies-literature

Aerobic exercise attenuates reinstatement of cocaine-seeking behavior and associated neuroadaptations in the prefrontal cortex.

Project description:Exercise has recently been suggested as an attractive alternative to pharmacotherapy for treating drug addiction. The goal of this study was to determine, using an animal model, whether aerobic exercise may block reinstatement of cocaine-seeking and its underlying neurobiology (i.e., neuronal signaling in the prefrontal cortex).Following acquisition and 10 days of 24-hour access to cocaine (1.5 mg/kg/infusion) or saline under a discrete trial procedure (four infusions/hr), rats began a 14-day abstinence period. During this period, rats were either given access to a running-wheel for 2-hours each day or placed in similar boxes with the wheel locked. Cocaine-seeking was assessed following the 14th day of abstinence using a within-session extinction/cue-induced reinstatement procedure. Neuronal activity was assessed by examining phosphorylated levels of extracellular signal-regulated kinase (pERK) using Western blot analysis.Wheel running reduced cocaine-seeking during both extinction and reinstatement. Cocaine-seeking was positively associated with pERK levels in the prefrontal cortex. Although pERK levels were not different among saline controls, in the cocaine group, pERK levels were significantly decreased by exercise.Aerobic exercise may reduce relapse vulnerability by preventing the increase in cocaine-seeking and associated neuroadaptations in the prefrontal cortex that develop over an abstinence period.

| S-EPMC2949528 | biostudies-literature

Stress-induced vulnerability to develop cocaine addiction depends on cofilin modulation.

Project description:Actin dynamics in dendritic spines can be associated with the neurobiological mechanisms supporting the comorbidity between stress exposure and cocaine increase rewards. The actin cytoskeleton remodeling in the nucleus accumbens (NA) has been implicated in the expression of stress-induced cross-sensitization with cocaine. The present study evaluates the involvement of cofilin, a direct regulator of actin dynamics, in the impact of stress on vulnerability to cocaine addiction. We assess whether the neurobiological mechanisms that modulate repeated-cocaine administration also occur in a chronic restraint stress-induced cocaine self-administration model. We also determine if chronic stress induces alterations in dendritic spines through dysregulation of cofilin activity in the NA core. Here, we show that the inhibition of cofilin expression in the NA core using viral short-hairpin RNA is sufficient to prevent the cocaine sensitization induced by chronic stress. The reduced cofilin levels also impede a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor surface expression enhancement and promote the reduction of head diameter in animals pre-exposed to stress after a cocaine challenge in the NA core. Moreover, downregulation of cofilin expression prevents facilitation of the acquisition of cocaine self-administration (SA) in male rats pre-exposed to chronic stress without modifying performance in sucrose SA. These findings reveal a novel, crucial role for cofilin in the neurobiological mechanisms underpinning the comorbidity between stress exposure and addiction-related disorders.

| S-EPMC8209265 | biostudies-literature

Hypothalamic proteoglycan syndecan-3 is a novel cocaine addiction resilience factor.

Project description:Proteoglycans like syndecan-3 have complex signaling roles in addition to their function as structural components of the extracellular matrix. Here, we show that syndecan-3 in the lateral hypothalamus has an unexpected new role in limiting compulsive cocaine intake. In particular, we observe that syndecan-3 null mice self-administer greater amounts of cocaine than wild-type mice. This effect can be rescued by re-expression of syndecan-3 in the lateral hypothalamus with an adeno-associated viral vector. Adeno-associated viral vector delivery of syndecan-3 to the lateral hypothalamus also reduces motivation for cocaine in normal mice. Syndecan-3 limits cocaine intake by modulating the effects of glial-cell-line-derived neurotrophic factor, which uses syndecan-3 as an alternative receptor. Our findings indicate syndecan-3-dependent signaling as a novel therapeutic target for the treatment of cocaine addiction.

| S-EPMC3709481 | biostudies-literature

Role of neuronal Xlr4 gene expression in cocaine addiction vulnerability: a microarray study in medial prefrontal cortex and Nucleus Accumbens of C57 and DBA mice.

Project description:Although several studies have been performed in rodents, non-human primates and humans, the biological basis of vulnerability to develop cocaine addiction remains largely unknown. Exposure to critical early events (as repeated cross fostering (RCF)) has been reported to increase sensitivity to cocaine in adult C57BL/6J female mice. Here we reasoned that by comparing the RCF-induced genes expression alterations in the NAc of adult mice (3 months of age) from two inbred strains (C57 and DBA), we could be able to identify critical genes underlying the adult behavioral phenotype. By a microarray analysis of gene expression (Agilent paltform)in the NAc of adult animals we found, among the several genes modulated, only 2 genes, the X-linked lymphocyte-regulated 4a and 4b (Xlr4a, Xlr4b), that were simultaneously modulated by the early experience in the two strains, but, notably, in opposite direction. All together, these data strongly indicate a critical role for Xlr4, a new yet unexplored candidate gene, in mediating vulnerability to cocaine addiction in mouse.

2021-12-01 | GSE124036 | GEO

Motivated cocaine seeking lead to transgenerational epigenetic inheritance of vulnerability to cocaine addiction

Project description:Familial transmission and high heritability of liability for drug abuse has been demonstrated by large scale epidemiological and twin studies, but the role of pre-existing susceptibility to addiction is still not clear. Our data show that F1 and F2 offspring sired by rats with high motivation for drug reinforcement and drug intake during cocaine self-administration maintained their ancestor’s addict-like behavior. This paternal transmission of drug addiction is an acquired trait that is dependent on cocaine induced high motivation in F0. Reduced representation bisulfite sequencing of F0 and F1 sperm DNA reveal a few persistent epigenetic changes in genes that critically regulate early development and morphogenesis. These epigenetic traits may underlie alterations in the neurological basis that lead to the transmission of cocaine motivation. Our results reveal the epigenetic transgenerational inheritance of drug craving and provide a potential etiology in cocaine abuse vulnerability.

2017-03-17 | GSE72401 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data