5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra.
Axonal release of serotonin (5-hydroxytryptamine, 5-HT) in the CNS is typically regulated by presynaptic 5-HT autoreceptors. Release of 5-HT in substantia nigra pars reticulata (SNr), a principal output from the basal ganglia, has seemed an interesting exception to this rule. The SNr receives one of...
Huvudupphovsmän: | , , |
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Materialtyp: | Journal article |
Språk: | English |
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2010
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_version_ | 1826292149448081408 |
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author | Threlfell, S Greenfield, S Cragg, S |
author_facet | Threlfell, S Greenfield, S Cragg, S |
author_sort | Threlfell, S |
collection | OXFORD |
description | Axonal release of serotonin (5-hydroxytryptamine, 5-HT) in the CNS is typically regulated by presynaptic 5-HT autoreceptors. Release of 5-HT in substantia nigra pars reticulata (SNr), a principal output from the basal ganglia, has seemed an interesting exception to this rule. The SNr receives one of the highest densities of 5-HT innervation in mammalian brain and yet negative feedback regulation of axonal 5-HT release by endogenous 5-HT has not been identified here. We explored whether we could identify autoregulation of 5-HT release by 5-HT(1B) receptors in rat SNr slices using fast-scan cyclic voltammetry at carbon-fiber microelectrodes to detect 5-HT release evoked by discrete stimuli (50 Hz, 20 pulses) paired over short intervals (1-10 s) within which any autoreceptor control should occur. Evoked 5-HT release exhibited short-term depression after an initial stimulus that recovered by 10 s. Antagonists for 5-HT(1B) receptors, isamoltane (1 microM) or SB 224-289 (1 microM), did not modify release during a stimulus train, but rather, they modestly relieved depression of subsequent release evoked after a short delay (< or =2 s). Release was not modified by antagonists for GABA (picrotoxin, 100 microM, saclofen, 50 microM) or histamine-H(3) (thioperamide, 10 microM) receptors. These data indicate that 5-HT release can activate a 5-HT(1B)-receptor autoinhibition of subsequent release, which is mediated directly via 5-HT axons and not via GABAergic or histaminergic inputs. These data reveal that 5-HT release in SNr is not devoid of autoreceptor regulation by endogenous 5-HT, but rather is under modest control which only weakly limits 5-HT signaling. |
first_indexed | 2024-03-07T03:10:14Z |
format | Journal article |
id | oxford-uuid:b3f1ad2a-a9d5-402f-9853-8a7c86d0ea49 |
institution | University of Oxford |
language | English |
last_indexed | 2024-03-07T03:10:14Z |
publishDate | 2010 |
record_format | dspace |
spelling | oxford-uuid:b3f1ad2a-a9d5-402f-9853-8a7c86d0ea492022-03-27T04:22:43Z5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:b3f1ad2a-a9d5-402f-9853-8a7c86d0ea49EnglishSymplectic Elements at Oxford2010Threlfell, SGreenfield, SCragg, SAxonal release of serotonin (5-hydroxytryptamine, 5-HT) in the CNS is typically regulated by presynaptic 5-HT autoreceptors. Release of 5-HT in substantia nigra pars reticulata (SNr), a principal output from the basal ganglia, has seemed an interesting exception to this rule. The SNr receives one of the highest densities of 5-HT innervation in mammalian brain and yet negative feedback regulation of axonal 5-HT release by endogenous 5-HT has not been identified here. We explored whether we could identify autoregulation of 5-HT release by 5-HT(1B) receptors in rat SNr slices using fast-scan cyclic voltammetry at carbon-fiber microelectrodes to detect 5-HT release evoked by discrete stimuli (50 Hz, 20 pulses) paired over short intervals (1-10 s) within which any autoreceptor control should occur. Evoked 5-HT release exhibited short-term depression after an initial stimulus that recovered by 10 s. Antagonists for 5-HT(1B) receptors, isamoltane (1 microM) or SB 224-289 (1 microM), did not modify release during a stimulus train, but rather, they modestly relieved depression of subsequent release evoked after a short delay (< or =2 s). Release was not modified by antagonists for GABA (picrotoxin, 100 microM, saclofen, 50 microM) or histamine-H(3) (thioperamide, 10 microM) receptors. These data indicate that 5-HT release can activate a 5-HT(1B)-receptor autoinhibition of subsequent release, which is mediated directly via 5-HT axons and not via GABAergic or histaminergic inputs. These data reveal that 5-HT release in SNr is not devoid of autoreceptor regulation by endogenous 5-HT, but rather is under modest control which only weakly limits 5-HT signaling. |
spellingShingle | Threlfell, S Greenfield, S Cragg, S 5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra. |
title | 5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra. |
title_full | 5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra. |
title_fullStr | 5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra. |
title_full_unstemmed | 5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra. |
title_short | 5-HT(1B) receptor regulation of serotonin (5-HT) release by endogenous 5-HT in the substantia nigra. |
title_sort | 5 ht 1b receptor regulation of serotonin 5 ht release by endogenous 5 ht in the substantia nigra |
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