Dual control of dorsal raphe serotonergic neurons by GABA B receptors. Electrophysiological and microdialysis studies

Dual control of dorsal raphe serotonergic neurons by GABA B receptors. Electrophysiological and... We assessed the role of GABAB receptors in the control of serotonergic (5‐HT) neurons of the dorsal raphe nucleus (DRN) by using microdialysis in vivo and intra‐ and extracellular recording in vitro in the rat. The GABAB agonist R(+)baclofen (but not the inactive S(‐)enantiomer) enhanced the 5‐HT output in the DRN (4.7‐fold at 15 mg/kg s.c.) and, to a much lesser extent, striatum of unanesthetized rats. Phaclofen (2 mg/kg s.c.) antagonized the effects of 6 mg/kg R(+)baclofen in dorsal striatum. Using dual‐probe microdialysis, R(+)baclofen (0.1–100 μM) applied in the DRN enhanced the local 5‐HT output (4.5‐fold at 100 μM) but decreased that in striatum at 100 μM. At concentrations higher than 100 μM there was a moderate decrement in the elevation of 5‐HT in the DRN. In midbrain slices, bath R(+)baclofen exerted a biphasic effect on DRN 5‐HT neurons. Consistent with a reduced striatal 5‐HT release when infused in the DRN, R(+)baclofen (0.1–30 μM) induced an outward current in 5‐HT neurons (IC50 = 1.4 μM). Lower R(+)baclofen concentrations (0.01–1 μM) preferentially reduced GABAergic inhibitory postsynaptic currents induced by N‐methyl‐D‐aspartate (20 μM) in 5‐HT neurons (IC50 = 72 nM). Using extracellular recordings, R(+)baclofen (300 nM) enhanced the ability of NMDA to induce firing in a subpopulation of serotonergic neurons. These results are consistent with a preferential activation by a low concentration of R(+)baclofen of presynaptic GABAB receptors on GABAergic afferents that could disinhibit 5‐HT neurons and increase 5‐HT release. Synapse 36:21–34, 2000. © 2000 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Synapse Wiley

Dual control of dorsal raphe serotonergic neurons by GABA B receptors. Electrophysiological and microdialysis studies

Loading next page...
 
/lp/wiley/dual-control-of-dorsal-raphe-serotonergic-neurons-by-gaba-b-receptors-YfglkCLNCs
Publisher
Wiley
Copyright
Copyright © 2000 Wiley‐Liss, Inc.
ISSN
0887-4476
eISSN
1098-2396
DOI
10.1002/(SICI)1098-2396(200004)36:1<21::AID-SYN3>3.0.CO;2-D
pmid
10700023
Publisher site
See Article on Publisher Site

Abstract

We assessed the role of GABAB receptors in the control of serotonergic (5‐HT) neurons of the dorsal raphe nucleus (DRN) by using microdialysis in vivo and intra‐ and extracellular recording in vitro in the rat. The GABAB agonist R(+)baclofen (but not the inactive S(‐)enantiomer) enhanced the 5‐HT output in the DRN (4.7‐fold at 15 mg/kg s.c.) and, to a much lesser extent, striatum of unanesthetized rats. Phaclofen (2 mg/kg s.c.) antagonized the effects of 6 mg/kg R(+)baclofen in dorsal striatum. Using dual‐probe microdialysis, R(+)baclofen (0.1–100 μM) applied in the DRN enhanced the local 5‐HT output (4.5‐fold at 100 μM) but decreased that in striatum at 100 μM. At concentrations higher than 100 μM there was a moderate decrement in the elevation of 5‐HT in the DRN. In midbrain slices, bath R(+)baclofen exerted a biphasic effect on DRN 5‐HT neurons. Consistent with a reduced striatal 5‐HT release when infused in the DRN, R(+)baclofen (0.1–30 μM) induced an outward current in 5‐HT neurons (IC50 = 1.4 μM). Lower R(+)baclofen concentrations (0.01–1 μM) preferentially reduced GABAergic inhibitory postsynaptic currents induced by N‐methyl‐D‐aspartate (20 μM) in 5‐HT neurons (IC50 = 72 nM). Using extracellular recordings, R(+)baclofen (300 nM) enhanced the ability of NMDA to induce firing in a subpopulation of serotonergic neurons. These results are consistent with a preferential activation by a low concentration of R(+)baclofen of presynaptic GABAB receptors on GABAergic afferents that could disinhibit 5‐HT neurons and increase 5‐HT release. Synapse 36:21–34, 2000. © 2000 Wiley‐Liss, Inc.

Journal

SynapseWiley

Published: Apr 1, 2000

References

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create folders to
organize your research

Export folders, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off