In Vivo Modulation of the Activity of Pyramidal Neurons in the Rat Medial Prefrontal Cortex by 5-HT2A Receptors: Relationship to Thalamocortical Afferents

Puig, M. Victoria

doi:10.1093/cercor/13.8.870

Cited by 191 publications

(207 citation statements)

References 63 publications

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“…Activation of 5-HT 2A receptors depolarizes pyramidal neurons (Araneda and Andrade, 1991;Tanaka and North, 1993) and enhances their firing activity (Puig et al, 2003), an effect that may involve glutamate release from thalamocortical afferents (Marek et al, 2001). In contrast, activation of 5-HT 1A receptors hyperpolarizes pyramidal neurons (Araneda and Andrade, 1991; Ashby et al, 1994) and activation of 5-HT 1B/1D heteroceptors can decrease release of glutamate and/or other excitatory amino acids (Marcoli et al, 1999;Maura et al, 1998;Tanaka and North, 1993).…”

Section: Discussionmentioning

confidence: 99%

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Marek

Martı́n-Ruiz

Abo

et al. 2005

Neuropsychopharmacol

112

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The addition of low doses of atypical antipsychotic drugs, which saturate 5-HT 2A receptors, enhances the therapeutic effect of selective serotonin (5-hydroxytryptamine; 5-HT) reuptake inhibitors (SSRIs) in patients with major depression as well as treatment-refractory obsessive-compulsive disorder. The purpose of the present studies was to test the effects of combined treatment with a low dose of a highly selective 5-HT 2A receptor antagonist (M100907; formerly MDL 100,907) and low doses of a SSRI using a behavioral screen in rodents (the differential-reinforcement-of low rate 72-s schedule of reinforcement; DRL 72-s) which previously has been shown to be sensitive both to 5-HT 2 antagonists and SSRIs. M100907 has a B100-fold or greater selectivity at 5-HT 2A receptors vs other 5-HT receptor subtypes, and would not be expected to appreciably occupy non-5-HT 2A receptors at doses below 100 mg/kg. M100907 increased the reinforcement rate, decreased the response rate, and shifted the inter-response time distributions to the right in a pattern characteristic of antidepressant drugs. In addition, a positive synergistic interaction occurred when testing low doses of the 5-HT 2A receptor antagonist (6.25-12.5 mg/kg) with clinically relevant doses of the SSRI fluoxetine (2.5-5 mg/kg), which both exerted minimal antidepressant-like effects by themselves. In vivo microdialysis study revealed that a low dose of M100907 (12.5 mg/kg) did not elevate extracellular 5-HT levels in the prefrontal cortex over those observed with fluoxetine alone (5 mg/kg). These results will be discussed in the context that the combined blockade of 5-HT 2A receptors and serotonin transporters (SERT) may result in greater efficacy in treating neuropsychiatric syndromes than blocking either site alone.

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Section: Discussionmentioning

confidence: 99%

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Marek

Martı́n-Ruiz

Abo

et al. 2005

Neuropsychopharmacol

112

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“…The activation of 5-HT 1A receptors in the PFC inhibits the neuronal output of pyramidal neurons by activation of a hyperpolarizing potassium current; 5-HT 2A facilitates output through a reduction of potassium conductance, reduction of the after-hyperpolarization, and increase in excitatory postsynaptic currents and discharge rate (Aghajanian and Marek, 1997;Andrade and Nicoll, 1987;Araneda and Andrade, 1991;Tanaka and North, 1993). Inhibitory effects of 5-HT 2A receptors on pyramidal cell activity have also been reported (Ashby et al, 1994;Puig et al, 2003;Zhou and Hablitz, 1999).…”

Section: Introductionmentioning

confidence: 97%

Dissociable Contribution of 5-HT1A and 5-HT2A Receptors in the Medial Prefrontal Cortex to Different Aspects of Executive Control such as Impulsivity and Compulsive Perseveration in Rats

Carli

Baviera

Invernizzi

et al. 2005

Neuropsychopharmacol

165

157

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Serotonin (5-HT) receptors are increasingly recognized as major targets for cognitive enhancement in schizophrenia. Several lines of evidence suggest a pathophysiological role for glutamate NMDA receptors in the prefrontal cortex in schizophrenia and associated disorders in attention and executive functioning. We investigated how the interactions between 5-HT 1A and 5-HT 2A and glutamate NMDA receptor mechanisms in the medial prefrontal cortex (mPFC) contribute to the control of different aspects of attentional performance. Rats were trained on a five-choice serial reaction time (5-CSRT) task, which provides indices of attentional functioning (percentage of correct responses), executive control (measured by anticipatory and perseverative responses), and speed. The competitive NMDA receptor antagonist CPP (50 ng/side) was infused directly into the mPFC 5 min after infusion of either 8-OH-DPAT (30 and 100 ng/side) or M100907 (100 and 300 ng/side) into the same brain area. Impairments in attentional functioning induced by CPP were completely abolished by both doses of 8-OH-DPAT or M100907. In addition, M100907 abolished the CPP-induced anticipatory responding but had no effects on perseverative over-responding, while 8-OH-DPAT reduced the perseverative over-responding but had no effects on anticipatory responding induced by CPP. The selective 5-HT 1A receptor antagonist WAY100635 (30 ng/side) antagonized the effects of 8-OH-DPAT (100 ng/side). 8-OH-DPAT at 30 ng/side reduced the latency of correct responses in controls and CPPinjected rats and lowered the percentage of omissions in CPP-injected rats. The data show that 5-HT 1A and 5-HT 2A receptors in the mPFC exert opposing actions on attentional functioning and demonstrate a dissociable contribution of 5-HT 1A and 5-HT 2A receptors in the mPFC to different aspects of executive control such as impulsivity and compulsive perseveration.

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“…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] .…”

Section: Leao's Cortical Spreading Depressionmentioning

confidence: 98%

“…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] . Activation of 5-HT1A receptors hyperpolarizes, whereas activation of 5-HT2A receptors depolarizes pyramidal neurons [47][48][49] . On the other hand, 5-HT2A receptors are expressed in large and 5-HT3 receptors in small GABAergic interneurons [50] .…”

Section: Leao's Cortical Spreading Depressionmentioning

confidence: 99%

“…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%

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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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In Vivo Modulation of the Activity of Pyramidal Neurons in the Rat Medial Prefrontal Cortex by 5-HT2A Receptors: Relationship to Thalamocortical Afferents

Cited by 191 publications

References 63 publications

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

The Selective 5-HT2A Receptor Antagonist M100907 Enhances Antidepressant-Like Behavioral Effects of the SSRI Fluoxetine

Dissociable Contribution of 5-HT1A and 5-HT2A Receptors in the Medial Prefrontal Cortex to Different Aspects of Executive Control such as Impulsivity and Compulsive Perseveration in Rats

Role of cortical spreading depression in the pathophysiology of migraine

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