The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety
The periaqueductal gray (PAG) is a significant modulator of both analgesic and fear behaviors in both humans and rodents, but the underlying circuitry responsible for these two phenotypes is incompletely understood. Importantly, it is not known if there is a way to produce analgesia without anxiety...
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| Format: | Article |
| Language: | English |
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Society for Neuroscience
2020
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| Online Access: | https://hdl.handle.net/1721.1/126481 |
| _version_ | 1811090485402402816 |
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| author | Taylor, Norman E. Pei, JunZhu Zhang, Jie Vlasov, Ksenia Davis, Trevor Taylor, Emma Weng, Feng-Ju Van Dort, Christa J. Solt, Ken Brown, Emery Neal |
| author2 | Picower Institute for Learning and Memory |
| author_facet | Picower Institute for Learning and Memory Taylor, Norman E. Pei, JunZhu Zhang, Jie Vlasov, Ksenia Davis, Trevor Taylor, Emma Weng, Feng-Ju Van Dort, Christa J. Solt, Ken Brown, Emery Neal |
| author_sort | Taylor, Norman E. |
| collection | MIT |
| description | The periaqueductal gray (PAG) is a significant modulator of both analgesic and fear behaviors in both humans and rodents, but the underlying circuitry responsible for these two phenotypes is incompletely understood. Importantly, it is not known if there is a way to produce analgesia without anxiety by targeting the PAG, as modulation of glutamate or GABA neurons in this area initiates both antinociceptive and anxiogenic behavior. While dopamine (DA) neurons in the ventrolateral PAG (vlPAG)/dorsal raphe display a supraspinal antinociceptive effect, their influence on anxiety and fear are unknown. Using DAT-cre and Vglut2-cre male mice, we introduced designer receptors exclusively activated by designer drugs (DREADD) to DA and glutamate neurons within the vlPAG using viral-mediated delivery and found that levels of analgesia were significant and quantitatively similar when DA and glutamate neurons were selectively stimulated. Activation of glutamatergic neurons, however, reliably produced higher indices of anxiety, with increased freezing time and more time spent in the safety of a dark enclosure. In contrast, animals in which PAG/dorsal raphe DA neurons were stimulated failed to show fear behaviors. DA-mediated antinociception was inhibitable by haloperidol and was sufficient to prevent persistent inflammatory pain induced by carrageenan. In summary, only activation of DA neurons in the PAG/dorsal raphe produced profound analgesia without signs of anxiety, indicating that PAG/dorsal raphe DA neurons are an important target involved in analgesia that may lead to new treatments for pain. |
| first_indexed | 2024-09-23T14:46:54Z |
| format | Article |
| id | mit-1721.1/126481 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:46:54Z |
| publishDate | 2020 |
| publisher | Society for Neuroscience |
| record_format | dspace |
| spelling | mit-1721.1/1264812022-10-01T22:25:26Z The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety Taylor, Norman E. Pei, JunZhu Zhang, Jie Vlasov, Ksenia Davis, Trevor Taylor, Emma Weng, Feng-Ju Van Dort, Christa J. Solt, Ken Brown, Emery Neal Picower Institute for Learning and Memory Massachusetts Institute of Technology. Department of Brain and Cognitive Sciences The periaqueductal gray (PAG) is a significant modulator of both analgesic and fear behaviors in both humans and rodents, but the underlying circuitry responsible for these two phenotypes is incompletely understood. Importantly, it is not known if there is a way to produce analgesia without anxiety by targeting the PAG, as modulation of glutamate or GABA neurons in this area initiates both antinociceptive and anxiogenic behavior. While dopamine (DA) neurons in the ventrolateral PAG (vlPAG)/dorsal raphe display a supraspinal antinociceptive effect, their influence on anxiety and fear are unknown. Using DAT-cre and Vglut2-cre male mice, we introduced designer receptors exclusively activated by designer drugs (DREADD) to DA and glutamate neurons within the vlPAG using viral-mediated delivery and found that levels of analgesia were significant and quantitatively similar when DA and glutamate neurons were selectively stimulated. Activation of glutamatergic neurons, however, reliably produced higher indices of anxiety, with increased freezing time and more time spent in the safety of a dark enclosure. In contrast, animals in which PAG/dorsal raphe DA neurons were stimulated failed to show fear behaviors. DA-mediated antinociception was inhibitable by haloperidol and was sufficient to prevent persistent inflammatory pain induced by carrageenan. In summary, only activation of DA neurons in the PAG/dorsal raphe produced profound analgesia without signs of anxiety, indicating that PAG/dorsal raphe DA neurons are an important target involved in analgesia that may lead to new treatments for pain. 2020-08-05T20:57:38Z 2020-08-05T20:57:38Z 2019-01 2019-01 2019-09-30T15:55:10Z Article http://purl.org/eprint/type/JournalArticle 2373-2822 https://hdl.handle.net/1721.1/126481 Taylor, Norman E. "The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety." eNeuro 6, 1 (January 2019): e0018-18.2019 © 2019 Taylor et al en http://dx.doi.org/10.1523/eneuro.0018-18.2019 eNeuro Creative Commons Attribution 4.0 International license https://creativecommons.org/licenses/by/4.0/ application/pdf Society for Neuroscience Society for Neurocience |
| spellingShingle | Taylor, Norman E. Pei, JunZhu Zhang, Jie Vlasov, Ksenia Davis, Trevor Taylor, Emma Weng, Feng-Ju Van Dort, Christa J. Solt, Ken Brown, Emery Neal The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety |
| title | The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety |
| title_full | The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety |
| title_fullStr | The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety |
| title_full_unstemmed | The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety |
| title_short | The Role of Glutamatergic and Dopaminergic Neurons in the Periaqueductal Gray/Dorsal Raphe: Separating Analgesia and Anxiety |
| title_sort | role of glutamatergic and dopaminergic neurons in the periaqueductal gray dorsal raphe separating analgesia and anxiety |
| url | https://hdl.handle.net/1721.1/126481 |
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