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...

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Huvudupphovsmän: Threlfell, S, Greenfield, S, Cragg, S
Materialtyp: Journal article
Språk:English
Publicerad: 2010
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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.
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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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AT greenfields 5ht1breceptorregulationofserotonin5htreleasebyendogenous5htinthesubstantianigra
AT craggs 5ht1breceptorregulationofserotonin5htreleasebyendogenous5htinthesubstantianigra