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Dual control of dorsal raphe serotonergic neurons by GABA B receptors. Electrophysiological and microdialysis studies
Author(s) -
Abellán María T.,
Jolas Thierry,
Aghajanian George K.,
Artigas Francesc
Publication year - 2000
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/(sici)1098-2396(200004)36:1<21::aid-syn3>3.0.co;2-d
Subject(s) - microdialysis , dorsal raphe nucleus , baclofen , serotonergic , chemistry , gabab receptor , striatum , raphe nuclei , agonist , autoreceptor , pharmacology , medicine , neuroscience , serotonin , receptor , extracellular , biology , dopamine , biochemistry
We assessed the role of GABA B 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 GABA B 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 (IC 50 = 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 (IC 50 = 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 GABA B receptors on GABAergic afferents that could disinhibit 5‐HT neurons and increase 5‐HT release. Synapse 36:21–34, 2000. © 2000 Wiley‐Liss, Inc.