Transcriptomic Effects of Paternal Cocaine-seeking on the Reward Circuitry of Male Offspring
Abstract In previous research, it has been established that a strong incentive motivation for cocaine, rather than the drug itself, can contribute to the intergenerational inheritance of cocaine addiction susceptibility in descendants. However, the precise impact of paternal cocaine-seeking on the reward circuitry of offspring remains not fully elucidated. To differentiate between cocaine-exposure and cocaine-seeking factors, we employed two distinct paternal cocaine acquisition paradigms: cocaine self-administration and yoked administration. These paradigms were used to generate the F1 generation, along with a control group receiving saline treatment. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naive conditions and after cocaine self-administration. Our study revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine-exposure. Conversely, the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) showed alterations that were more closely linked to the paternal voluntary cocaine-seeking experience. Based on transcriptomic analysis, measurements of dopamine levels (DOPA), and cellular activation analysis, we propose that the VTA-dStr pathway plays a pivotal role in mediating the effects of paternal voluntary cocaine-seeking on offspring. Furthermore, we identified potential transcriptomic regulatory mechanisms mediated by key transcriptional factors. Our findings provide a comprehensive overview of the transcriptional changes resulting from paternal highly-motivated cocaine-seeking. Importantly, our data highlight vulnerable neurocircuitry and novel gene candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 27. Feb. Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Le, Qiumin [VerfasserIn] |
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| doi: |
10.21203/rs.3.rs-3202898/v1 |
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| PPN (Katalog-ID): |
XRA041076605 |
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| 520 | |a Abstract In previous research, it has been established that a strong incentive motivation for cocaine, rather than the drug itself, can contribute to the intergenerational inheritance of cocaine addiction susceptibility in descendants. However, the precise impact of paternal cocaine-seeking on the reward circuitry of offspring remains not fully elucidated. To differentiate between cocaine-exposure and cocaine-seeking factors, we employed two distinct paternal cocaine acquisition paradigms: cocaine self-administration and yoked administration. These paradigms were used to generate the F1 generation, along with a control group receiving saline treatment. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naive conditions and after cocaine self-administration. Our study revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine-exposure. Conversely, the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) showed alterations that were more closely linked to the paternal voluntary cocaine-seeking experience. Based on transcriptomic analysis, measurements of dopamine levels (DOPA), and cellular activation analysis, we propose that the VTA-dStr pathway plays a pivotal role in mediating the effects of paternal voluntary cocaine-seeking on offspring. Furthermore, we identified potential transcriptomic regulatory mechanisms mediated by key transcriptional factors. Our findings provide a comprehensive overview of the transcriptional changes resulting from paternal highly-motivated cocaine-seeking. Importantly, our data highlight vulnerable neurocircuitry and novel gene candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction. | ||
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| 700 | 1 | |a Huang, Nan |4 aut | |
| 700 | 1 | |a Cui, Jian |4 aut | |
| 700 | 1 | |a Fan, Guangyuan |4 aut | |
| 700 | 1 | |a Pan, Tao |4 aut | |
| 700 | 1 | |a Han, Kunxiu |4 aut | |
| 700 | 1 | |a Xu, Kailiang |4 aut | |
| 700 | 1 | |a Jiang, Changyou |0 (orcid)0000-0002-2157-6098 |4 aut | |
| 700 | 1 | |a Liu, Xing |4 aut | |
| 700 | 1 | |a Wang, Feifei |0 (orcid)0000-0002-2351-6873 |4 aut | |
| 700 | 1 | |a Ma, Lan |0 (orcid)0000-0001-9034-5472 |4 aut | |
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