5-Hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex

Araneda, Ricardo C.; Andrade, Rodrigo

doi:10.1016/0306-4522(91)90128-b

Cited by 570 publications

(452 citation statements)

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“…Application of a saturating concentration of the 5-HT 1A agonist 8-OH-DPAT (20 μM) produced a significant reduction of the firing rate (32.4 ± 4.7%, n = 7), while the saturating concentration of 5-HT 2A/C agonist α-Me-5HT (20 μM) significantly increased the firing rate (35.8 ± 5.2%, n = 7), consistent with previous results (Araneda and Andrade, 1991). However, at low concentrations, both 8-OH-DPAT (1 μM) and α-Me-5HT (0.8 μM) failed to induce significant changes in AP firing (8-OH-DPAT: 4-5% reduction; α-Me-5HT: 2-7% increase, Figure 1E).…”

Section: -Ht 1a and 5-ht 2a/c Receptors By Interacting With Nmda Resupporting

confidence: 91%

“…NIH-PA Author Manuscript NIH-PA Author Manuscript μM) significantly increased the firing rate (35.8 ± 5.2%, n = 7), consistent with previous results (Araneda and Andrade, 1991). However, at low concentrations, both 8-OH-DPAT (1 μM) and α-Me-5HT (0.8 μM) failed to induce significant changes in AP firing (8-OH-DPAT: 4-5% reduction; α-Me-5HT: 2-7% increase, Figure 1E).…”

Section: Nih-pa Author Manuscriptsupporting

confidence: 90%

“…5-HT 1A receptor activation can induce a membrane hyperpolarization in hippocampal neurons (Andrade et al, 1986), probably by opening inward rectifying potassium channels (Colino and Halliwell, 1987), inhibiting voltage-dependent calcium channels (Penington and Kelly, 1990), or activating the TWIK-1 type of two-pore domain potassium channels (Deng et al, 2007). In contrast, 5-HT 2 receptor activation can induce a membrane depolarization in cortical neurons (Araneda and Andrade, 1991;Aghajanian and Marek 1997), probably by inhibiting an inwardly rectifying potassium conductance (North and Uchimura, 1989) or activating a cation nonselective current (Haj-Dahmane and Andrade, 1996).…”

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Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex

Zhong

Yuen

Yan

2008

Molecular and Cellular Neuroscience

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Both serotonin and NMDA signaling in prefrontal cortex (PFC) are implicated in mental disorders, including depression and anxiety. To understand their potential contributions to PFC neuronal excitability, we examined the effect of co-activation of 5-HT and NMDA receptors on action potential firing elicited by depolarizing current injection in PFC pyramidal neurons. In the presence of NMDA, a low concentration of the 5-HT 1A agonist 8-OH-DPAT substantially reduced the number of spikes, and a low concentration of the 5-HT 2A/C agonist α-Me-5HT significantly enhanced it, while both agonists were ineffective when applied alone. The 8-OH-DPAT effect on firing was mediated by inhibition of protein kinase A (PKA), whereas the α-Me-5HT effect was mediated by activation of protein kinase C (PKC). Moreover, the extracellular signal-regulated kinase (ERK), a signaling molecule downstream of PKA and PKC, was involved in both 5-HT 1A and 5-HT 2A/C modulation of neuronal excitability. Biochemical evidence showed that 5-HT 1A decreased, whereas 5-HT 2A/C increased the activation of ERK in an NMDA-dependent manner. In animals exposed to acutely stress, the enhancing effect of 5-HT 2A/C on firing was lost, while the decreasing effect of 5-HT 1A on firing was intact. Concomitantly, the effect of 5-HT 2A/C , but not 5-HT 1A , on ERK activation was abolished in stressed animals. Taken together, our results demonstrate that distinct 5-HT receptor subtypes, by interacting with NMDA receptors, differentially regulate PFC neuronal firing, and the complex effects of 5-HT receptors on excitability are selectively altered under stressful conditions, which are often associated with mental disorders.Keywords 5-HT 1A receptor; 5-HT 2 receptor; NMDA receptor; action potential firing; ERK; stress; prefrontal cortexThe prefrontal cortex (PFC) receives a dense serotonergic innervation from the raphe nuclei (Smiley and Goldman-Rakic, 1996). The serotonergic system plays an important role in regulating PFC functions, including emotional control, cognitive behaviors and working memory (Williams et al., 1996;Buhot 1997;Williams et al., 2002). Aberrant serotonin system * Correspondence should be addressed to ZhenYan, Ph.D., Department of Physiology and Biophysics, State University of New York at Buffalo, 124 Sherman Hall, Buffalo, NY, 14214, USA. Email: zhenyan@buffalo.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. This PDF receipt will only be used as the basis for generating PubMed Central (PMC) documents. PMC documents will be made available for review after conversion (approx. 2-3 weeks time)...

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Section: -Ht 1a and 5-ht 2a/c Receptors By Interacting With Nmda Resupporting

confidence: 91%

Section: Nih-pa Author Manuscriptsupporting

confidence: 90%

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confidence: 99%

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Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex

Zhong

Yuen

Yan

2008

Molecular and Cellular Neuroscience

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“…), where both receptor subtypes display opposing effects when they were stimulated (Araneda and Andrade, 1991). It is also of note that the partial 5-HT 1A agonist buspirone increased PPI in rats (Johansson et al, 1995), despite the many reports that more specific and full 5-HT 1A agonists disrupt PPI in rats (for review see Geyer et al (2001)).…”

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confidence: 99%

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Vollenweider

Csomor

Knappe

et al. 2007

Neuropsychopharmacol

155

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Schizophrenia patients exhibit impairments in prepulse inhibition (PPI) of the startle response. Hallucinogenic 5-HT 2A receptor agonists are used for animal models of schizophrenia because they mimic some symptoms of schizophrenia in humans and induce PPI deficits in animals. Nevertheless, one report indicates that the 5-HT 2A receptor agonist psilocybin increases PPI in healthy humans. Hence, we investigated these inconsistent results by assessing the dose-dependent effects of psilocybin on PPI in healthy humans. Sixteen subjects each received placebo or 115, 215, and 315 mg/kg of psilocybin at 4-week intervals in a randomized and counterbalanced order. PPI at 30-, 60-, 120-, 240-, and 2000-ms interstimulus intervals (ISIs) was measured 90 and 165 min after drug intake, coinciding with the peak and post-peak effects of psilocybin. The effects of psilocybin on psychopathological core dimensions and sustained attention were assessed by the Altered States of Consciousness Rating Scale (5D-ASC) and the Frankfurt Attention Inventory (FAIR). Psilocybin dosedependently reduced PPI at short (30 ms), had no effect at medium (60 ms), and increased PPI at long (120-2000 ms) ISIs, without affecting startle reactivity or habituation. Psilocybin dose-dependently impaired sustained attention and increased all 5D-ASC scores with exception of Auditory Alterations. Moreover, psilocybin-induced impairments in sustained attention performance were positively correlated with reduced PPI at the 30 ms ISI and not with the concomitant increases in PPI observed at long ISIs. These results confirm the psilocybin-induced increase in PPI at long ISIs and reveal that psilocybin also produces a decrease in PPI at short ISIs that is correlated with impaired attention and consistent with deficient PPI in schizophrenia.

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“…Moreover, several studies have reported that the spread of SD stops where white matter [45,46] . Consistent with these observations, we also demonstrated that the velocity of cortical SD gradually decreases from the dorsal to the ventral cortical areas of the insular cortex, in which the volume distribution of astrocyte is known to gradually increase.Recently, we have also demonstrated that the brain serotonergic system, which is known to modulate the excitability of cortical neurons through activation of several receptor subtypes, in particular, 5-HT1A, 5-HT2A, and 5-HT3 receptors [47][48][49] , contributes to the propagation of cortical SD. Pyramidal neurons in the cerebral cortex express 5-HT1A and 5-HT2A receptors, which exert opposing effects on the excitability and firing activity of pyramidal neurons [47,49] .…”

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confidence: 98%

Role of cortical spreading depression in the pathophysiology of migraine

2014

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A migraine is a recurring neurological disorder characterized by unilateral, intense, and pulsatile headaches. In one-third of migraine patients, the attacks are preceded by a visual aura, such as a slowly-propagating scintillating scotoma. Migraine aura is thought to be a result of the neurovascular phenomenon of cortical spreading depression (SD), a self-propagating wave of depolarization that spreads across the cerebral cortex. Several animal experiments have demonstrated that cortical SD causes intracranial neurogenic infl ammation around the meningeal blood vessels, such as plasma protein extravasation and pro-inflammatory peptide release. Cortical SD has also been reported to activate both peripheral and central trigeminal nociceptive pathways. Although several issues remain to be resolved, recent evidence suggests that cortical SD could be the initial trigger of intracranial neurogenic inflammation, which then contributes to migraine headaches via subsequent activation of trigeminal afferents.Keywords: cortical spreading depression; migraine; neurogenic inflammation; PET; trigeminal nociceptive pathway ·Review· IntroductionCortical spreading depression (SD), described first by Leao [1] , is a self-propagating wave of transient neuronal/ glial membrane depolarization that is accompanied by a transient negative shift of the direct current (DC) potential [2] and temporal elevation of cerebral blood flow (CBF) [3,4] throughout the cerebral hemisphere at a rate of 2-5 mm/ min [1, 5,6] . The rate of spreading correlates with the observed spread of the aura of a classical migraine [7] , which is characterized by a spot of fl ickering light that appears near the center of the visual field and then gradually expands outward [8][9][10] . Recently, cortical SD has been hypothesized to be the initial event involved in migraine headaches.Moskowitz et al. [11,12] proposed that pro-inflammatory peptides, such as substance P and calcitonin generelated peptide (CGRP), released from trigeminocervical nerve terminals in response to some unknown stimulation, probably cortical SD, induces vasodilation and plasma protein extravasation. Such neurogenic inflammation is thought to trigger a headache via stimulation of trigeminal afferents. Consistent with this hypothesis, cortical SD induced intracranial neurogenic inflammation around the meningeal blood vessels [13][14][15] , and subsequent activation of both peripheral [16] and central [17] trigeminal nociceptive pathways has been described. Here, we review the experimental evidence mainly from neurophysiological studies that has advanced the understanding of whether and how the neurovascular phenomenon of cortical SD causes intracranial neurogenic inflammation, and subsequently participates in triggering a migraine headache. Migraine PathophysiologyA migraine is a recurring neurological disorder characterized Yilong Cui, et al . Role of cortical spreading depression in the pathophysiology of migraine 813 by unilateral, intense, and pulsatile headaches lasting 4-72 h [18] , a...

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5-Hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex

Cited by 570 publications

References 44 publications

Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex

Modulation of Neuronal Excitability by Serotonin-NMDA Interactions in Prefrontal Cortex

The Effects of the Preferential 5-HT2A Agonist Psilocybin on Prepulse Inhibition of Startle in Healthy Human Volunteers Depend on Interstimulus Interval

Role of cortical spreading depression in the pathophysiology of migraine

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