Dopaminergic inhibition of striatal GABA release after 6-hydroxydopamine

L. Hársing, Michael J. Zigmond

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

We have examined the regulation of striatal GABA release by endogenous dopamine in rats with partial degeneration of dopamine-containing neurons. 6-Hydroxydopamine was administered into the lateral ventricles or medial forebrain bundle. Either 3 days or 3 weeks later, slices of neostriatum were prepared, preloaded with [3H]GABA, and superfused in order to measure [3H]GABA overflow in response to electrical stimulation (8 Hz). The loss of dopaminergic terminals was estimated by measuring tissue levels of dopamine. The impact of endogenous dopamine on [3H]GABA was evaluated by measuring the ability of sulpiride, a D2 dopamine receptor antagonist, to increase the depolarization-induced [3H]GABA overflow. In non-treated or vehicle-pretreated rat neostriatum. sulpiride (10 μM) increased the depolarization-induced [3H]GABA overflow to 193% of control. Three days after lesioning, the stimulatory effect of sulpiride on [3H]GABA overflow was identical to that seen in control rats so long as the loss of tissue dopamine did not exceed 60%, although with larger lesions the sulpiride-induced response was reduced. Three weeks after lesioning, however, the stimulatory effect of sulpiride on electrically evoked [3H]GABA overflow remained at the level seen in control tissue even in cases where tissue dopamine was reduced to 13% of normal. In contrast, no sulpiride-induced increase in [3H]GABA overflow was detected 3 weeks after nearly complete lesions which reduced tissue dopamine to 2% of normal. These data suggest that short- and long-term compensatory changes maintain dopaminergic control over GABAergic projection neurons and interneurons until the loss of dopamine innervation is almost complete.

Original languageEnglish
Pages (from-to)142-145
Number of pages4
JournalBrain Research
Volume738
Issue number1
DOIs
Publication statusPublished - Oct 28 1996

Fingerprint

Corpus Striatum
Oxidopamine
gamma-Aminobutyric Acid
Sulpiride
Dopamine
Neostriatum
Medial Forebrain Bundle
GABAergic Neurons
Lateral Ventricles
Dopaminergic Neurons
Interneurons
Electric Stimulation

Keywords

  • 6-hydroxydopamine
  • brain slice
  • dopamine
  • GABA release
  • neostriatum
  • Parkinson's disease

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Dopaminergic inhibition of striatal GABA release after 6-hydroxydopamine. / Hársing, L.; Zigmond, Michael J.

In: Brain Research, Vol. 738, No. 1, 28.10.1996, p. 142-145.

Research output: Contribution to journalArticle

Hársing, L. ; Zigmond, Michael J. / Dopaminergic inhibition of striatal GABA release after 6-hydroxydopamine. In: Brain Research. 1996 ; Vol. 738, No. 1. pp. 142-145.
@article{52b10128b49a4915a46016d3967b5f42,
title = "Dopaminergic inhibition of striatal GABA release after 6-hydroxydopamine",
abstract = "We have examined the regulation of striatal GABA release by endogenous dopamine in rats with partial degeneration of dopamine-containing neurons. 6-Hydroxydopamine was administered into the lateral ventricles or medial forebrain bundle. Either 3 days or 3 weeks later, slices of neostriatum were prepared, preloaded with [3H]GABA, and superfused in order to measure [3H]GABA overflow in response to electrical stimulation (8 Hz). The loss of dopaminergic terminals was estimated by measuring tissue levels of dopamine. The impact of endogenous dopamine on [3H]GABA was evaluated by measuring the ability of sulpiride, a D2 dopamine receptor antagonist, to increase the depolarization-induced [3H]GABA overflow. In non-treated or vehicle-pretreated rat neostriatum. sulpiride (10 μM) increased the depolarization-induced [3H]GABA overflow to 193{\%} of control. Three days after lesioning, the stimulatory effect of sulpiride on [3H]GABA overflow was identical to that seen in control rats so long as the loss of tissue dopamine did not exceed 60{\%}, although with larger lesions the sulpiride-induced response was reduced. Three weeks after lesioning, however, the stimulatory effect of sulpiride on electrically evoked [3H]GABA overflow remained at the level seen in control tissue even in cases where tissue dopamine was reduced to 13{\%} of normal. In contrast, no sulpiride-induced increase in [3H]GABA overflow was detected 3 weeks after nearly complete lesions which reduced tissue dopamine to 2{\%} of normal. These data suggest that short- and long-term compensatory changes maintain dopaminergic control over GABAergic projection neurons and interneurons until the loss of dopamine innervation is almost complete.",
keywords = "6-hydroxydopamine, brain slice, dopamine, GABA release, neostriatum, Parkinson's disease",
author = "L. H{\'a}rsing and Zigmond, {Michael J.}",
year = "1996",
month = "10",
day = "28",
doi = "10.1016/0006-8993(96)00956-0",
language = "English",
volume = "738",
pages = "142--145",
journal = "Brain Research",
issn = "0006-8993",
publisher = "Elsevier",
number = "1",

}

TY - JOUR

T1 - Dopaminergic inhibition of striatal GABA release after 6-hydroxydopamine

AU - Hársing, L.

AU - Zigmond, Michael J.

PY - 1996/10/28

Y1 - 1996/10/28

N2 - We have examined the regulation of striatal GABA release by endogenous dopamine in rats with partial degeneration of dopamine-containing neurons. 6-Hydroxydopamine was administered into the lateral ventricles or medial forebrain bundle. Either 3 days or 3 weeks later, slices of neostriatum were prepared, preloaded with [3H]GABA, and superfused in order to measure [3H]GABA overflow in response to electrical stimulation (8 Hz). The loss of dopaminergic terminals was estimated by measuring tissue levels of dopamine. The impact of endogenous dopamine on [3H]GABA was evaluated by measuring the ability of sulpiride, a D2 dopamine receptor antagonist, to increase the depolarization-induced [3H]GABA overflow. In non-treated or vehicle-pretreated rat neostriatum. sulpiride (10 μM) increased the depolarization-induced [3H]GABA overflow to 193% of control. Three days after lesioning, the stimulatory effect of sulpiride on [3H]GABA overflow was identical to that seen in control rats so long as the loss of tissue dopamine did not exceed 60%, although with larger lesions the sulpiride-induced response was reduced. Three weeks after lesioning, however, the stimulatory effect of sulpiride on electrically evoked [3H]GABA overflow remained at the level seen in control tissue even in cases where tissue dopamine was reduced to 13% of normal. In contrast, no sulpiride-induced increase in [3H]GABA overflow was detected 3 weeks after nearly complete lesions which reduced tissue dopamine to 2% of normal. These data suggest that short- and long-term compensatory changes maintain dopaminergic control over GABAergic projection neurons and interneurons until the loss of dopamine innervation is almost complete.

AB - We have examined the regulation of striatal GABA release by endogenous dopamine in rats with partial degeneration of dopamine-containing neurons. 6-Hydroxydopamine was administered into the lateral ventricles or medial forebrain bundle. Either 3 days or 3 weeks later, slices of neostriatum were prepared, preloaded with [3H]GABA, and superfused in order to measure [3H]GABA overflow in response to electrical stimulation (8 Hz). The loss of dopaminergic terminals was estimated by measuring tissue levels of dopamine. The impact of endogenous dopamine on [3H]GABA was evaluated by measuring the ability of sulpiride, a D2 dopamine receptor antagonist, to increase the depolarization-induced [3H]GABA overflow. In non-treated or vehicle-pretreated rat neostriatum. sulpiride (10 μM) increased the depolarization-induced [3H]GABA overflow to 193% of control. Three days after lesioning, the stimulatory effect of sulpiride on [3H]GABA overflow was identical to that seen in control rats so long as the loss of tissue dopamine did not exceed 60%, although with larger lesions the sulpiride-induced response was reduced. Three weeks after lesioning, however, the stimulatory effect of sulpiride on electrically evoked [3H]GABA overflow remained at the level seen in control tissue even in cases where tissue dopamine was reduced to 13% of normal. In contrast, no sulpiride-induced increase in [3H]GABA overflow was detected 3 weeks after nearly complete lesions which reduced tissue dopamine to 2% of normal. These data suggest that short- and long-term compensatory changes maintain dopaminergic control over GABAergic projection neurons and interneurons until the loss of dopamine innervation is almost complete.

KW - 6-hydroxydopamine

KW - brain slice

KW - dopamine

KW - GABA release

KW - neostriatum

KW - Parkinson's disease

UR - http://www.scopus.com/inward/record.url?scp=0030605165&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030605165&partnerID=8YFLogxK

U2 - 10.1016/0006-8993(96)00956-0

DO - 10.1016/0006-8993(96)00956-0

M3 - Article

VL - 738

SP - 142

EP - 145

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1

ER -