National Institute on Drug Abuse genomics consortium white paper: Coordinating efforts between human and animal addiction studies

Cates, Hannah M.; Benca-Bachman, Chelsie E.; Guglielmo, Giordano de; Schoenrock, Sarah A.; Shu, Chen; Kallupi, Marsida

doi:10.1111/gbb.12577

Cited by 12 publications

(9 citation statements)

References 68 publications

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“…Synchronizing gene expression from 70 precarious post-mortem human data with precise and carefully controlled studies in 71 animal models affords the opportunity to pinpoint and characterize certain neuro-72 molecular sources of variability; it may also help quantify the pathogenicity of a 73 specific behavior with a diseased state. Such insights will also inform the ongoing 74 dialogue surrounding comparative cross-species approaches in bio-behavioral 75 research 10 . 76…”

Section: Introduction 37mentioning

confidence: 99%

Meso-limbic Gene Expression Findings from Mouse Cocaine Self-Administration Recapitulate Human Cocaine Use Disorder

Huggett

Bubier

Chesler

et al. 2020

Preprint

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Animal models of drug use have been employed for over 100 years to facilitate the 10 identification of mechanisms governing human substance use and addiction. Most 11 cross-species research on drug use/addiction examines behavioral overlap, but 12 studies assessing neuro-molecular correspondence are lacking. Our study utilized 13 transcriptome-wide data from the hippocampus and ventral tegmental area 14 (VTA)/midbrain from a total of 35 human males with cocaine use disorder/controls 15 and 49 male C57BL/6J cocaine/saline administering/exposed mice. We 16hypothesized that individual genes (differential expression) and systems of co-17 expressed genes (gene networks) would demonstrate appreciable overlap across 18 mouse cocaine self-administration and human cocaine use disorder. We found 19modest, but significant associations between differentially expressed genes 20 associated with cocaine self-administration (short access) and cocaine use disorder 21 within meso-limbic circuitry, but non-robust associations with mouse models of 22 acute cocaine exposure, (cocaine) context re-exposure and cocaine + context re-23 exposure. Investigating systems of co-expressed genes, we also found several 24 validated gene networks with weak to moderate conservation between 25 cocaine/saline self-administering mice and disordered cocaine users/controls. The 26 most conserved hippocampal and VTA gene networks demonstrated substantial 27 overlap (2,029 common genes) and included novel and previously implicated 28 targets of cocaine use/addiction. Lastly, we conducted expression-based phenome-29 wide association studies of the nine common hub genes across conserved gene 30 networks and found that they were associated with dopamine/serotonin function, 31cocaine self-administration and other relevant mouse traits. Overall, our study 32 identified and characterized homologous transcriptional effects between mouse 33 models of cocaine self-administration and human cocaine use disorder that may 34 serve as a benchmark for future research. 35 36

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Section: Introduction 37mentioning

confidence: 99%

Meso-limbic Gene Expression Findings from Mouse Cocaine Self-Administration Recapitulate Human Cocaine Use Disorder

Huggett

Bubier

Chesler

et al. 2020

Preprint

View full text Add to dashboard Cite

show abstract

“…Synchronizing gene expression from precarious postmortem human data with carefully controlled studies in animal models affords the opportunity to pinpoint and characterize neuromolecular sources of variability. Such insights will inform the ongoing diaglogue surrounding comparative cross‐species approaches in biobehavioral research 10 …”

Section: Introductionmentioning

confidence: 99%

Do gene expression findings from mouse models of cocaine use recapitulate human cocaine use disorder in reward circuitry?

Huggett

Bubier

Chesler

et al. 2020

Genes Brain and Behavior

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Animal models of drug use have investigated possible mechanisms governing human substance use traits for over 100 years. Most cross‐species research on drug use/addiction examines behavioral overlap, but studies assessing neuromolecular (e.g. RNA) correspondence are lacking. Our study utilized transcriptome‐wide data from the hippocampus and ventral tegmental area (VTA)/midbrain from a total of 35 human males with cocaine use disorder/controls and 49 male C57BL/6J cocaine/saline administering/exposed mice. We hypothesized differential expressed genes and systems of co‐expressed genes (gene networks) would show appreciable overlap across mouse cocaine self‐administration and human cocaine use disorder. We found modest, but significant relationships between differentially expressed genes associated with cocaine self‐administration (short access) and cocaine use disorder within reward circuitry. Differentially expressed genes underlying models of acute cocaine exposure (cocaine), context re‐exposure and cocaine + context re‐exposure were not consistently associated with human CUD across brain regions. Investigating systems of co‐expressed genes, we found several validated gene networks with weak to moderate conservation between cocaine/saline self‐administering mice and disordered cocaine users/controls. The most conserved hippocampal and VTA gene networks demonstrated substantial overlap (2029 common genes) and included both novel and previously implicated targets for cocaine use/addiction. Lastly, we conducted (expression‐based) phenome‐wide association studies of the nine common hub genes across conserved gene networks. Common hub genes were associated with dopamine/serotonin function, cocaine self‐administration and other relevant mouse traits. Overall, our study pinpointed and characterized conserved brain‐related RNA patterns across mouse cocaine self‐administration and human cocaine use disorder. We offer recommendations for future research and add to the dialogue surrounding pre‐clinical animal research for human disease.

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“…The devastating epidemic of opioid addiction in the United States is enormously costly, in both human life and economically [1]. Genetics plays a major role in addiction vulnerability, but cannot account for this recent rise in opioid abuse, so environmental factors (e.g., increased access to prescription opioids) must contribute [2][3][4]. Notably, substance use disorders are most prevalent among those who experienced early life poverty and trauma, and given their overrepresentation in this population, women are especially vulnerable [5][6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

On the early life origins of vulnerability to opioid addiction

et al. 2019

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The origins and neural bases of the current opioid addiction epidemic are unclear. Genetics plays a major role in addiction vulnerability, but cannot account for the recent exponential rise in opioid abuse, so environmental factors must contribute. Individuals with history of early life adversity (ELA) are disproportionately prone to opioid addiction, yet whether ELA interacts with factors such as increased access to opioids to directly influence brain development and function, and cause opioid addiction vulnerability, is unknown. We simulated ELA in female rats and this led to a striking opioid addiction-like phenotype. This was characterized by resistance to extinction, increased relapse-like behavior, and, as in addicted humans, major increases in opioid economic demand. By contrast, seeking of a less salient natural reward was unaffected by ELA, whereas demand for highly palatable treats was augmented. These discoveries provide novel insights into the origins and nature of reward circuit malfunction that may set the stage for addiction.

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National Institute on Drug Abuse genomics consortium white paper: Coordinating efforts between human and animal addiction studies

Cited by 12 publications

References 68 publications

Meso-limbic Gene Expression Findings from Mouse Cocaine Self-Administration Recapitulate Human Cocaine Use Disorder

Meso-limbic Gene Expression Findings from Mouse Cocaine Self-Administration Recapitulate Human Cocaine Use Disorder

Do gene expression findings from mouse models of cocaine use recapitulate human cocaine use disorder in reward circuitry?

On the early life origins of vulnerability to opioid addiction

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