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Please use this identifier to cite or link to this item: http://hdl.handle.net/10261/33137
Title: Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism
Authors: Martín-Ruiz, Raúl; Puig, M. Victoria; Celada, Pau ; Shapiro, David A.; Roth, Bryan L.; Mengod Los Arcos, Guadalupe ; Artigas, Francesc
Keywords: 5-hydroxytryptamine
5-HT1A receptors
5-HT2A receptors
dorsal raphe nucleus
medial prefrontal cortex
single-unit recordings
Issue Date: 15-Dec-2001
Publisher: Society for Neuroscience
Citation: Journal of Neuroscience 21 (24) : 9856–9866 (2001)
Abstract: We examined the in vivo effects of the hallucinogen 4-iodo-2,5-dimethoxyamphetamine (DOI). DOI suppressed the firing rate of 7 of 12 dorsal raphe (DR) serotonergic (5-HT) neurons and partially inhibited the rest (ED(50) = 20 microg/kg, i.v.), an effect reversed by M100907 (5-HT(2A) antagonist) and picrotoxinin (GABA(A) antagonist). DOI (1 mg/kg, s.c.) reduced the 5-HT release in medial prefrontal cortex (mPFC) to 33 +/- 8% of baseline, an effect also antagonized by M100907. However, the local application of DOI in the mPFC increased 5-HT release (164 +/- 6% at 100 microm), an effect antagonized by tetrodotoxin, M100907, and BAY x 3702 (5-HT(1A) agonist) but not by SB 242084 (5-HT(2C) antagonist). The 5-HT increase was also reversed by NBQX (AMPA-KA antagonist) and 1S,3S-ACPD (mGluR 2/3 agonist) but not by MK-801 (NMDA antagonist). AMPA mimicked the 5-HT elevation produced by DOI. Likewise, the electrical-chemical stimulation of thalamocortical afferents and the local inhibition of glutamate uptake increased the 5-HT release through AMPA receptors. DOI application in mPFC increased the firing rate of a subgroup of 5-HT neurons (5 of 10), indicating an enhanced output of pyramidal neurons. Dual-label fluorescence confocal microscopic studies demonstrated colocalization of 5-HT(1A) and 5-HT(2A) receptors on individual cortical pyramidal neurons. Thus, DOI reduces the activity of ascending 5-HT neurons through a DR-based action and enhances serotonergic and glutamatergic transmission in mPFC through 5-HT(2A) and AMPA receptors. Because pyramidal neurons coexpress 5-HT(1A) and 5-HT(2A) receptors, DOI disrupts the balance between excitatory and inhibitory inputs and leads to an increased activity that may mediate its hallucinogenic action.
Description: Publicada errata en: Erratum: Control of serotonergic function in medial prefrontal cortex by serotonin-2A receptors through a glutamate-dependent mechanism (The Journal of Neuroscience (2001) (9856-9866)), Journal of Neuroscience 22(3): i (2002)
Publisher version (URL): http://www.jneurosci.org/content/21/24/9856.full
URI: http://hdl.handle.net/10261/33137
ISSN: 0270-6474
E-ISSN: 1529-2401
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