QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) A correction has been published Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (61) Citing Articles via Google Scholar Google Scholar Articles by Martín-Ruiz, R. Articles by Artigas, F. Search for Related Content PubMed PubMed Citation Articles by Martín-Ruiz, R. Articles by Artigas, F.

 Previous Article  |  Next Article 

The Journal of Neuroscience, December 15, 2001, 21(24):9856-9866

Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism

Raúl Martín-Ruiz¹, M. Victoria Puig¹, Pau Celada¹, David A. Shapiro², Bryan L. Roth², Guadalupe Mengod¹, and Francesc Artigas¹

¹ Department of Neurochemistry, Institut d' Investigacions Biomèdiques de Barcelona (Consejo Superior de Investigaciones Científicas), Institut d'Investigacions Biomèdiques August Pi i Sunyer, 08036 Barcelona, Spain, and ² Departments of Biochemistry, Neurosciences and Psychiatry, Case Western Reserve University Medical School, Cleveland, Ohio 44106

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 (ED₅₀ = 20 µg/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 µM), an effect antagonized by tetrodotoxin, M100907, and BAY × 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.

Key words: 5-hydroxytryptamine; 5-HT_1A receptors; 5-HT_2A receptors; AMPA; DOI; dorsal raphe nucleus; GABA; glutamate; hallucinogens; medial prefrontal cortex; microdialysis; mGluR; NMDA; single-unit recordings; thalamus

---

Copyright © 2001 Society for Neuroscience  0270-6474/01/21249856-11$05.00/0

This article has been cited by other articles:

				P. Weikop, J. Kehr, and J. Scheel-Kruger Reciprocal effects of combined administration of serotonin, noradrenaline and dopamine reuptake inhibitors on serotonin and dopamine levels in the rat prefrontal cortex: the role of 5-HT1A receptors J Psychopharmacol, November 1, 2007; 21(8): 795 - 804. [Abstract] [PDF]

				J. A. Gray and B. L. Roth Molecular Targets for Treating Cognitive Dysfunction in Schizophrenia Schizophr Bull, September 1, 2007; 33(5): 1100 - 1119. [Abstract] [Full Text] [PDF]

				J.-C. Beique, M. Imad, L. Mladenovic, J. A. Gingrich, and R. Andrade Mechanism of the 5-hydroxytryptamine 2A receptor-mediated facilitation of synaptic activity in prefrontal cortex PNAS, June 5, 2007; 104(23): 9870 - 9875. [Abstract] [Full Text] [PDF]

				R.-P. Behrendt Dysregulation of thalamic sensory 'transmission' in schizophrenia: neurochemical vulnerability to hallucinations J Psychopharmacol, May 1, 2006; 20(3): 356 - 372. [Abstract] [PDF]

				L. Diaz-Mataix, M. C. Scorza, A. Bortolozzi, M. Toth, P. Celada, and F. Artigas Involvement of 5-HT1A Receptors in Prefrontal Cortex in the Modulation of Dopaminergic Activity: Role in Atypical Antipsychotic Action J. Neurosci., November 23, 2005; 25(47): 10831 - 10843. [Abstract] [Full Text] [PDF]

				U. F. Bailer, G. K. Frank, S. E. Henry, J. C. Price, C. C. Meltzer, L. Weissfeld, C. A. Mathis, W. C. Drevets, A. Wagner, J. Hoge, et al. Altered Brain Serotonin 5-HT1A Receptor Binding After Recovery From Anorexia Nervosa Measured by Positron Emission Tomography and [Carbonyl11C]WAY-100635 Arch Gen Psychiatry, September 1, 2005; 62(9): 1032 - 1041. [Abstract] [Full Text] [PDF]

				M. V. Puig, F. Artigas, and P. Celada Modulation of the Activity of Pyramidal Neurons in Rat Prefrontal Cortex by Raphe Stimulation In Vivo: Involvement of Serotonin and GABA Cereb Cortex, January 1, 2005; 15(1): 1 - 14. [Abstract] [Full Text] [PDF]

				P. R. Albert and S. Lemonde 5-HT1A Receptors, Gene Repression, and Depression: Guilt by Association Neuroscientist, December 1, 2004; 10(6): 575 - 593. [Abstract] [PDF]

				N. Santana, A. Bortolozzi, J. Serrats, G. Mengod, and F. Artigas Expression of Serotonin1A and Serotonin2A Receptors in Pyramidal and GABAergic Neurons of the Rat Prefrontal Cortex Cereb Cortex, October 1, 2004; 14(10): 1100 - 1109. [Abstract] [Full Text] [PDF]

				Y. Zhang, T. S. Gray, D. N. D'Souza, G. A. Carrasco, K. J. Damjanoska, B. Dudas, F. Garcia, G. M. Zainelli, N. R. Sullivan Hanley, G. Battaglia, et al. Desensitization of 5-HT1A Receptors by 5-HT2A Receptors in Neuroendocrine Neurons in Vivo J. Pharmacol. Exp. Ther., July 1, 2004; 310(1): 59 - 66. [Abstract] [Full Text] [PDF]

				J.-C. Beique, B. Campbell, P. Perring, M. W. Hamblin, P. Walker, L. Mladenovic, and R. Andrade Serotonergic Regulation of Membrane Potential in Developing Rat Prefrontal Cortex: Coordinated Expression of 5-Hydroxytryptamine (5-HT)1A, 5-HT2A, and 5-HT7 Receptors J. Neurosci., May 19, 2004; 24(20): 4807 - 4817. [Abstract] [Full Text] [PDF]

				M. Amargos-Bosch, A. Bortolozzi, M. V. Puig, J. Serrats, A. Adell, P. Celada, M. Toth, G. Mengod, and F. Artigas Co-expression and In Vivo Interaction of Serotonin1A and Serotonin2A Receptors in Pyramidal Neurons of Prefrontal Cortex Cereb Cortex, March 1, 2004; 14(3): 281 - 299. [Abstract] [Full Text] [PDF]

				J. Gonzalez-Maeso, T. Yuen, B. J. Ebersole, E. Wurmbach, A. Lira, M. Zhou, N. Weisstaub, R. Hen, J. A. Gingrich, and S. C. Sealfon Transcriptome Fingerprints Distinguish Hallucinogenic and Nonhallucinogenic 5-Hydroxytryptamine 2A Receptor Agonist Effects in Mouse Somatosensory Cortex J. Neurosci., October 1, 2003; 23(26): 8836 - 8843. [Abstract] [Full Text] [PDF]

				Z. Xia, J. A. Gray, B. A. Compton-Toth, and B. L. Roth A Direct Interaction of PSD-95 with 5-HT2A Serotonin Receptors Regulates Receptor Trafficking and Signal Transduction J. Biol. Chem., June 6, 2003; 278(24): 21901 - 21908. [Abstract] [Full Text] [PDF]

				R. C. Foehring, J. F. M. van Brederode, G. A. Kinney, and W. J. Spain Serotonergic Modulation of Supragranular Neurons in Rat Sensorimotor Cortex J. Neurosci., September 15, 2002; 22(18): 8238 - 8250. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help