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| Hauptseite > Publikationsdatenbank > Dorsal BNST α 2A -Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors > print |
| Hauptseite > Publikationsdatenbank > Dorsal BNST α 2A -Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors > print |
| 001 | 857102 | ||
| 005 | 20230217124543.0 | ||
| 024 | 7 | _ | |a 10.1523/JNEUROSCI.0963-18.2018 |2 doi |
| 024 | 7 | _ | |a 0270-6474 |2 ISSN |
| 024 | 7 | _ | |a 1529-2401 |2 ISSN |
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| 037 | _ | _ | |a FZJ-2018-06356 |
| 082 | _ | _ | |a 610 |
| 100 | 1 | _ | |a Harris, Nicholas A. |0 0000-0002-5702-1342 |b 0 |
| 245 | _ | _ | |a Dorsal BNST α 2A -Adrenergic Receptors Produce HCN-Dependent Excitatory Actions That Initiate Anxiogenic Behaviors |
| 260 | _ | _ | |a Washington, DC |c 2018 |b Soc.69657 |
| 264 | _ | 1 | |3 online |2 Crossref |b Society for Neuroscience |c 2018-08-27 |
| 264 | _ | 1 | |3 print |2 Crossref |b Society for Neuroscience |c 2018-10-17 |
| 264 | _ | 1 | |3 print |2 Crossref |b Society for Neuroscience |c 2018-10-17 |
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| 520 | _ | _ | |a Stress is a precipitating agent in neuropsychiatric disease and initiates relapse to drug-seeking behavior in addicted patients. Targeting the stress system in protracted abstinence from drugs of abuse with anxiolytics may be an effective treatment modality for substance use disorders. α2A-adrenergic receptors (α2A-ARs) in extended amygdala structures play key roles in dampening stress responses. Contrary to early thinking, α2A-ARs are expressed at non-noradrenergic sites in the brain. These non-noradrenergic α2A-ARs play important roles in stress responses, but their cellular mechanisms of action are unclear. In humans, the α2A-AR agonist guanfacine reduces overall craving and uncouples craving from stress, yet minimally affects relapse, potentially due to competing actions in the brain. Here, we show that heteroceptor α2A-ARs postsynaptically enhance dorsal bed nucleus of the stria terminalis (dBNST) neuronal activity in mice of both sexes. This effect is mediated by hyperpolarization-activated cyclic nucleotide-gated cation channels because inhibition of these channels is necessary and sufficient for excitatory actions. Finally, this excitatory action is mimicked by clozapine-N-oxide activation of the Gi-coupled DREADD hM4Di in dBNST neurons and its activation elicits anxiety-like behavior in the elevated plus maze. Together, these data provide a framework for elucidating cell-specific actions of GPCR signaling and provide a potential mechanism whereby competing anxiogenic and anxiolytic actions of guanfacine may affect its clinical utility in the treatment of addiction. |
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| 700 | 1 | _ | |a Isaac, Austin T. |0 0000-0003-1306-4196 |b 1 |
| 700 | 1 | _ | |a Günther, Anne |0 0000-0001-8081-9275 |b 2 |
| 700 | 1 | _ | |a Merkel, Kevin |0 P:(DE-HGF)0 |b 3 |
| 700 | 1 | _ | |a Melchior, James |0 0000-0002-0223-077X |b 4 |
| 700 | 1 | _ | |a Xu, Michelle |0 P:(DE-HGF)0 |b 5 |
| 700 | 1 | _ | |a Eguakun, Eghosa |0 P:(DE-HGF)0 |b 6 |
| 700 | 1 | _ | |a Perez, Rafael |0 0000-0001-7788-4631 |b 7 |
| 700 | 1 | _ | |a Nabit, Brett P. |0 0000-0001-9459-2462 |b 8 |
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| 700 | 1 | _ | |a Gilsbach, Ralf |0 0000-0002-0895-1535 |b 10 |
| 700 | 1 | _ | |a Shonesy, Brian |0 P:(DE-HGF)0 |b 11 |
| 700 | 1 | _ | |a Hein, Lutz |0 0000-0003-1297-0007 |b 12 |
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| 700 | 1 | _ | |a Matthews, Robert |0 0000-0002-1235-3802 |b 15 |
| 700 | 1 | _ | |a Centanni, Samuel W. |0 0000-0002-3941-7677 |b 16 |
| 700 | 1 | _ | |a Winder, Danny G. |0 P:(DE-HGF)0 |b 17 |e Corresponding author |
| 773 | 1 | 8 | |a 10.1523/jneurosci.0963-18.2018 |b Society for Neuroscience |d 2018-08-27 |n 42 |p 8922-8942 |3 journal-article |2 Crossref |t The Journal of Neuroscience |v 38 |y 2018 |x 0270-6474 |
| 773 | _ | _ | |a 10.1523/JNEUROSCI.0963-18.2018 |g Vol. 38, no. 42, p. 8922 - 8942 |0 PERI:(DE-600)1475274-8 |n 42 |p 8922-8942 |t The journal of neuroscience |v 38 |y 2018 |x 0270-6474 |
| 856 | 4 | _ | |y Published on 2018-10-17. Available in OpenAccess from 2019-04-17. |u https://juser.fz-juelich.de/record/857102/files/8922.full.pdf |
| 856 | 4 | _ | |y Published on 2018-10-17. Available in OpenAccess from 2019-04-17. |x pdfa |u https://juser.fz-juelich.de/record/857102/files/8922.full.pdf?subformat=pdfa |
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