Serotonin2B receptors in the rat dorsal raphe nucleus exert a GABA-mediated tonic inhibitory control on serotonin neurons.
Experimental Neurology. 2019-01-01; 311: 57-66
DOI: 10.1016/j.expneurol.2018.09.015
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Cathala A(1), Devroye C(2), Drutel G(3), Revest JM(4), Artigas F(5), Spampinato U(6).
Author information:
(1)Inserm U1215, Neurocentre Magendie, Physiopathology and therapeutic
approaches of stress-related diseases, Bordeaux F-33000, France; Université de
Bordeaux, Bordeaux F-33000, France. Electronic address:
.
(2)Inserm U1215, Neurocentre Magendie, Physiopathology and therapeutic
approaches of stress-related diseases, Bordeaux F-33000, France; Université de
Bordeaux, Bordeaux F-33000, France. Electronic address: .
(3)Inserm U1215, Neurocentre Magendie, Physiopathology and therapeutic
approaches of stress-related diseases, Bordeaux F-33000, France; Université de
Bordeaux, Bordeaux F-33000, France. Electronic address:
.
(4)Inserm U1215, Neurocentre Magendie, Physiopathology and therapeutic
approaches of stress-related diseases, Bordeaux F-33000, France; Université de
Bordeaux, Bordeaux F-33000, France. Electronic address:
.
(5)Department of Neurochemistry and Neuropharmacology, Institut d’Investigacions
Biomèdiques de Barcelona, CSIC-IDIBAPS, Rosselló 161, 08036 Barcelona, Spain;
Centro de Investigación Biomédica en Red de Salud Mental (CIBERSAM), Spain.
Electronic address: .
(6)Inserm U1215, Neurocentre Magendie, Physiopathology and therapeutic
approaches of stress-related diseases, Bordeaux F-33000, France; Université de
Bordeaux, Bordeaux F-33000, France. Electronic address:
.
The central serotonin2B receptor (5-HT2BR) is a well-established modulator of
dopamine (DA) neuron activity in the rodent brain. Recent studies in rats have
shown that the effect of 5-HT2BR antagonists on accumbal and medial prefrontal
cortex (mPFC) DA outflow results from a primary action in the dorsal raphe
nucleus (DRN), where they activate 5-HT neurons innervating the mPFC. Although
the mechanisms underlying this interaction remain largely unknown, data in the
literature suggest the involvement of DRN GABAergic interneurons in the control
of 5-HT activity. The present study examined this hypothesis using in vivo
(intracerebral microdialysis) and in vitro (immunohistochemistry coupled to
reverse transcription-polymerase chain reaction) experimental approaches in
rats. Intraperitoneal (0.16 mg/kg) or intra-DRN (1 μM) administration of the
selective 5-HT2BR antagonist RS 127445 increased 5-HT outflow in both the DRN
and the mPFC, these effects being prevented by the intra-DRN perfusion of the
GABAA antagonist bicuculline (100 μM), as well as by the subcutaneous
(0.16 mg/kg) or the intra-DRN (0.1 μM) administration of the selective 5-HT1AR
antagonist WAY 100635. The increase in DRN 5-HT outflow induced by the intra-DRN
administration of the selective 5-HT reuptake inhibitor citalopram (0.1 μM) was
potentiated by the intra-DRN administration (0.5 μM) of RS 127445 only in the
absence of bicuculline perfusion. Finally, in vitro experiments revealed the
presence of the 5-HT2BR mRNA on DRN GABAergic interneurons. Altogether, these
results show that, in the rat DRN, 5-HT2BRs are located on GABAergic
interneurons, and exert a tonic inhibitory control on 5-HT neurons innervating
the mPFC.
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