Reciprocal innervation between serotonergic and GABAergic neurons in raphe nuclei of the rat

E. Bagdy, I. Kiraly, L. Hársing

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The slices were loaded with either [3H] serotonin or [3H]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABA(A) receptor agonist muscimol (3 to 30 μM) and the GABA(B) receptor agonist baclofen (30 and 100 μM) inhibited [3H]serotonin and [3H]GABA release. These effects of muscimol were reversed by the GABA(A) antagonists bicuculline (100 μM). The GABA(B) antagonist phaclofen (100 μM) also antagonized the baclofen-induced inhibition of [3H]serotonin and [3H]GABA release. Phaclofen by itself increased [3H]serotonin release but it did not alter [3H]GABA overflow. Muscimol (10 μM) and baclofen (100 μM) also inhibited [3H]serotonin release after depletion of GABAergic neurons by isoniazid pretreatment. These findings indicate the presence of postsynaptic GABA(A) and GABA(B) receptors located on serotonergic neurons. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.01 to 1 μM) and the 5-HT(1B) receptor agonist CGS-12066A (0.01 to 1 μM) inhibited the electrically stimulated [3H]serotonin and [3H]GABA release. The 5-HT(1A) antagonist WAY-100135 (1 μM) was without effect on [3H]serotonin and [3H]GABA efflux by itself but it reversed the 8-OH-DPAT-induced transmitter release inhibition. During KCl (22 mM)-induced depolarization, tetrodotoxin (1 μM) did not alter the inhibitory effect of CGS-12066A (1 μM) on [3H]GABA release, it did blocked, however, the ability of 8-OH-DPAT (1 μM) to reduce [3H]GABA efflux. After depletion of raphe serotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 μM) still inhibited [3H]GABA release whereas in serotonin-depleted slices, 8-OH-DPAT (1 μM) was without effect on the release. We conclude that reciprocal influence exists between serotonergic projection neurons and the GABAergic interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT(1A/B) and GABA(A/B) receptors. Both synaptic and non-synaptic neurotransmission may be operative in the 5-HTergic-GABAergic reciprocal interaction which may serve as a local tuning in the neural connection between cerebral cortex and midbrain raphe nuclei.

Original languageEnglish
Pages (from-to)1465-1473
Number of pages9
JournalNeurochemical Research
Volume25
Issue number11
DOIs
Publication statusPublished - 2000

Fingerprint

Serotonergic Neurons
GABAergic Neurons
Raphe Nuclei
gamma-Aminobutyric Acid
Neurons
Rats
Serotonin
8-Hydroxy-2-(di-n-propylamino)tetralin
Muscimol
Baclofen
GABA-B Receptors
GABA-B Receptor Antagonists
GABA-B Receptor Agonists
Receptor, Serotonin, 5-HT1B
Fenclonine
GABA-A Receptor Agonists
Mediodorsal Thalamic Nucleus
GABA-A Receptor Antagonists
Serotonin Antagonists
Receptor, Serotonin, 5-HT1A

Keywords

  • 5-HT(1A/1B) receptors
  • GABA release
  • GABA(A/B) receptors
  • Raphe nuclei
  • Serotonin release

ASJC Scopus subject areas

  • Neuroscience(all)
  • Biochemistry

Cite this

Reciprocal innervation between serotonergic and GABAergic neurons in raphe nuclei of the rat. / Bagdy, E.; Kiraly, I.; Hársing, L.

In: Neurochemical Research, Vol. 25, No. 11, 2000, p. 1465-1473.

Research output: Contribution to journalArticle

@article{0dd7bda8a4a34470be489879fd4e4c24,
title = "Reciprocal innervation between serotonergic and GABAergic neurons in raphe nuclei of the rat",
abstract = "Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The slices were loaded with either [3H] serotonin or [3H]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABA(A) receptor agonist muscimol (3 to 30 μM) and the GABA(B) receptor agonist baclofen (30 and 100 μM) inhibited [3H]serotonin and [3H]GABA release. These effects of muscimol were reversed by the GABA(A) antagonists bicuculline (100 μM). The GABA(B) antagonist phaclofen (100 μM) also antagonized the baclofen-induced inhibition of [3H]serotonin and [3H]GABA release. Phaclofen by itself increased [3H]serotonin release but it did not alter [3H]GABA overflow. Muscimol (10 μM) and baclofen (100 μM) also inhibited [3H]serotonin release after depletion of GABAergic neurons by isoniazid pretreatment. These findings indicate the presence of postsynaptic GABA(A) and GABA(B) receptors located on serotonergic neurons. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.01 to 1 μM) and the 5-HT(1B) receptor agonist CGS-12066A (0.01 to 1 μM) inhibited the electrically stimulated [3H]serotonin and [3H]GABA release. The 5-HT(1A) antagonist WAY-100135 (1 μM) was without effect on [3H]serotonin and [3H]GABA efflux by itself but it reversed the 8-OH-DPAT-induced transmitter release inhibition. During KCl (22 mM)-induced depolarization, tetrodotoxin (1 μM) did not alter the inhibitory effect of CGS-12066A (1 μM) on [3H]GABA release, it did blocked, however, the ability of 8-OH-DPAT (1 μM) to reduce [3H]GABA efflux. After depletion of raphe serotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 μM) still inhibited [3H]GABA release whereas in serotonin-depleted slices, 8-OH-DPAT (1 μM) was without effect on the release. We conclude that reciprocal influence exists between serotonergic projection neurons and the GABAergic interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT(1A/B) and GABA(A/B) receptors. Both synaptic and non-synaptic neurotransmission may be operative in the 5-HTergic-GABAergic reciprocal interaction which may serve as a local tuning in the neural connection between cerebral cortex and midbrain raphe nuclei.",
keywords = "5-HT(1A/1B) receptors, GABA release, GABA(A/B) receptors, Raphe nuclei, Serotonin release",
author = "E. Bagdy and I. Kiraly and L. H{\'a}rsing",
year = "2000",
doi = "10.1023/A:1007672008297",
language = "English",
volume = "25",
pages = "1465--1473",
journal = "Neurochemical Research",
issn = "0364-3190",
publisher = "Springer New York",
number = "11",

}

TY - JOUR

T1 - Reciprocal innervation between serotonergic and GABAergic neurons in raphe nuclei of the rat

AU - Bagdy, E.

AU - Kiraly, I.

AU - Hársing, L.

PY - 2000

Y1 - 2000

N2 - Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The slices were loaded with either [3H] serotonin or [3H]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABA(A) receptor agonist muscimol (3 to 30 μM) and the GABA(B) receptor agonist baclofen (30 and 100 μM) inhibited [3H]serotonin and [3H]GABA release. These effects of muscimol were reversed by the GABA(A) antagonists bicuculline (100 μM). The GABA(B) antagonist phaclofen (100 μM) also antagonized the baclofen-induced inhibition of [3H]serotonin and [3H]GABA release. Phaclofen by itself increased [3H]serotonin release but it did not alter [3H]GABA overflow. Muscimol (10 μM) and baclofen (100 μM) also inhibited [3H]serotonin release after depletion of GABAergic neurons by isoniazid pretreatment. These findings indicate the presence of postsynaptic GABA(A) and GABA(B) receptors located on serotonergic neurons. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.01 to 1 μM) and the 5-HT(1B) receptor agonist CGS-12066A (0.01 to 1 μM) inhibited the electrically stimulated [3H]serotonin and [3H]GABA release. The 5-HT(1A) antagonist WAY-100135 (1 μM) was without effect on [3H]serotonin and [3H]GABA efflux by itself but it reversed the 8-OH-DPAT-induced transmitter release inhibition. During KCl (22 mM)-induced depolarization, tetrodotoxin (1 μM) did not alter the inhibitory effect of CGS-12066A (1 μM) on [3H]GABA release, it did blocked, however, the ability of 8-OH-DPAT (1 μM) to reduce [3H]GABA efflux. After depletion of raphe serotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 μM) still inhibited [3H]GABA release whereas in serotonin-depleted slices, 8-OH-DPAT (1 μM) was without effect on the release. We conclude that reciprocal influence exists between serotonergic projection neurons and the GABAergic interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT(1A/B) and GABA(A/B) receptors. Both synaptic and non-synaptic neurotransmission may be operative in the 5-HTergic-GABAergic reciprocal interaction which may serve as a local tuning in the neural connection between cerebral cortex and midbrain raphe nuclei.

AB - Midbrain slices containing the dorsal and medial raphe nuclei were prepared from rat brain in order to study serotonergic-GABAergic interaction. The slices were loaded with either [3H] serotonin or [3H]GABA, superfused and the electrically induced efflux of radioactivity was determined. The GABA(A) receptor agonist muscimol (3 to 30 μM) and the GABA(B) receptor agonist baclofen (30 and 100 μM) inhibited [3H]serotonin and [3H]GABA release. These effects of muscimol were reversed by the GABA(A) antagonists bicuculline (100 μM). The GABA(B) antagonist phaclofen (100 μM) also antagonized the baclofen-induced inhibition of [3H]serotonin and [3H]GABA release. Phaclofen by itself increased [3H]serotonin release but it did not alter [3H]GABA overflow. Muscimol (10 μM) and baclofen (100 μM) also inhibited [3H]serotonin release after depletion of GABAergic neurons by isoniazid pretreatment. These findings indicate the presence of postsynaptic GABA(A) and GABA(B) receptors located on serotonergic neurons. The 5-HT(1A) receptor agonist 8-OH-DPAT (0.01 to 1 μM) and the 5-HT(1B) receptor agonist CGS-12066A (0.01 to 1 μM) inhibited the electrically stimulated [3H]serotonin and [3H]GABA release. The 5-HT(1A) antagonist WAY-100135 (1 μM) was without effect on [3H]serotonin and [3H]GABA efflux by itself but it reversed the 8-OH-DPAT-induced transmitter release inhibition. During KCl (22 mM)-induced depolarization, tetrodotoxin (1 μM) did not alter the inhibitory effect of CGS-12066A (1 μM) on [3H]GABA release, it did blocked, however, the ability of 8-OH-DPAT (1 μM) to reduce [3H]GABA efflux. After depletion of raphe serotonin neurons by p-chlorophenylalanine pretreatment, CGS-12066A (1 μM) still inhibited [3H]GABA release whereas in serotonin-depleted slices, 8-OH-DPAT (1 μM) was without effect on the release. We conclude that reciprocal influence exists between serotonergic projection neurons and the GABAergic interneurons or afferents in the raphe nuclei and these interactions may be mediated by 5-HT(1A/B) and GABA(A/B) receptors. Both synaptic and non-synaptic neurotransmission may be operative in the 5-HTergic-GABAergic reciprocal interaction which may serve as a local tuning in the neural connection between cerebral cortex and midbrain raphe nuclei.

KW - 5-HT(1A/1B) receptors

KW - GABA release

KW - GABA(A/B) receptors

KW - Raphe nuclei

KW - Serotonin release

UR - http://www.scopus.com/inward/record.url?scp=0033792971&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033792971&partnerID=8YFLogxK

U2 - 10.1023/A:1007672008297

DO - 10.1023/A:1007672008297

M3 - Article

C2 - 11071365

AN - SCOPUS:0033792971

VL - 25

SP - 1465

EP - 1473

JO - Neurochemical Research

JF - Neurochemical Research

SN - 0364-3190

IS - 11

ER -