In vivo electrophysiological and neurochemical effects of the selective 5-HT1A receptor agonist, F13640, at pre- and postsynaptic 5-HT1A receptors in the rat

Lladó-Pelfort, Laia; Assié, Marie Bernadette; Newman‐Tancredi, Adrian; Artigas, Francesc; Celada, Pau

doi:10.1007/s00213-011-2569-9

Cited by 42 publications

(25 citation statements)

References 61 publications

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“…Consistent with this, NLX-112 profoundly suppresses serotonergic neuron activity, as indicated by microdialysis studies in which it inhibited striatal serotonin levels by over 60% on both lesioned and non-lesioned sides of the brain ( Figure 5-6). This is similar to NLX-112's effects on serotonin release previously reported for frontal cortex and hippocampus (Llado-Pelfort et al, 2012) and consistent with its efficacious suppression of Raphe serotonin neuron electrical activity (Llado-Pelfort et al, 2012).…”

Section: Nlx-112 Exhibits Potent Anti-dyskinetic Activity In Ratsupporting

confidence: 84%

“…NLX-112 exhibits nanomolar affinity and exceptional selectivity for 5-HT 1A receptors and has been extensively characterized as a potential treatment for chronic pain (Colpaert, 2006). Like F13714, NLX-112 potently activates 5-HT 1A raphe autoreceptors but, in addition, also activates cortical heteroreceptors (Llado-Pelfort et al, 2012). The latter activity is associated with beneficial effects on mood (antidepressant action) and cognition (facilitation of cortical dopamine release), so NLX-112 could potentially alleviate both LID and some non-motor symptoms of PD, including mood deficits such as anxiety and depression.…”

Section: Introductionmentioning

confidence: 98%

See 1 more Smart Citation

NLX-112, a novel 5-HT 1A receptor agonist for the treatment of l -DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat

Iderberg

McCreary

Varney

et al. 2015

Experimental Neurology

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Section: Nlx-112 Exhibits Potent Anti-dyskinetic Activity In Ratsupporting

confidence: 84%

Section: Introductionmentioning

confidence: 98%

NLX-112, a novel 5-HT 1A receptor agonist for the treatment of l -DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat

Iderberg

McCreary

Varney

et al. 2015

Experimental Neurology

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“…This effect is strikingly different from the effect of 5‐HT 1A receptor activation in the prefrontal cortex where pyramidal cells are disinhibited due to a presumed 5‐HT 1A receptor‐mediated inhibition of interneurons (Lladó‐Pelfort et al . ). While the Lladó‐Pelfort study indicates localization of 5‐HT 1A receptors on inhibitory rather than excitatory cell types in the prefrontal cortex, our data demonstrate a strong inhibition of pyramidal cells in the hippocampus.…”

Section: Discussionmentioning

confidence: 97%

5‐Hydroxytryptamine_1A receptor‐activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation

Johnston

McBain

Fisahn

2014

The Journal of Physiology

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Key pointsr Rhythmic activity in the gamma frequency range in the hippocampus is modulated by neurotransmitters such as serotonin, dopamine and histamine.r Multiple different serotonin receptors are expressed in the hippocampus. r Here we show that serotonin suppresses hippocampal gamma oscillations via activation of the receptor 5-HT 1A .r The cellular cause for suppressed gamma oscillations is the 5-HT 1A receptor-induced hyperpolarization and afterpolarization frequency reduction of pyramidal cells, but not of parvalbumin-positive interneurons.r The pyramidal cell hyperpolarization is mediated by an inwardly rectifying current mediated by the Kir3 potassium channel known to couple to 5-HT 1A , which also results in decreased firing frequency.Abstract Rhythmic cortical neuronal oscillations in the gamma frequency band (30-80 Hz, gamma oscillations) have been associated with cognitive processes such as sensory perception and integration, attention, learning, and memory. Gamma oscillations are disrupted in disorders for which cognitive deficits are hallmark symptoms such as schizophrenia and Alzheimer's disease. In vitro, various neurotransmitters have been found to modulate gamma oscillations. Serotonin (5-HT) has long been known to be important for both behavioural and cognitive functions such as learning and memory. Multiple 5-HT receptor subtypes are expressed in the CA3 region of the hippocampus and high doses of 5-HT reduce the power of induced gamma oscillations. Hypothesizing that 5-HT may have cell-and receptor subtype-specific modulatory effects, we investigated the receptor subtypes, cell types and cellular mechanisms engaged by 5-HT in the modulation of gamma oscillations in mice and rats. We found that 5-HT decreases the power of kainate-induced hippocampal gamma oscillations in both species via the 5-HT 1A receptor subtype. Whole-cell patch clamp recordings demonstrated that this decrease was caused by a hyperpolarization of CA3 pyramidal cells and a reduction of their firing frequency, but not by alteration of inhibitory neurotransmission. Finally, our results show that the effect on pyramidal cells is mediated via the G protein-coupled receptor inwardly rectifying potassium channel Kir3. Our findings suggest this novel cellular mechanism as a potential target for therapies that are aimed at alleviating cognitive decline by helping the brain to maintain or re-establish normal gamma oscillation levels in neuropsychiatric and neurodegenerative disorders.

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“…However, these agents appear to have a more complex effect on cortical (PFC) pyramidal neurons, with either a biphasic effect (increase in firing activity at lower doses followed by decrease at higher doses) or affecting different neuronal populations in a distinct manner (most neurons excited by 5-HT 1A agonists) (Borsini et al, 1995; Hajos et al, 1999; Diaz-Mataix et al, 2006; Lladó-Pelfort et al, 2010, 2012a,b). Thus, the systemic administration of the selective 5-HT 1A receptor agonist 8-OH-DPAT increased the firing activity of pyramidal neurons and reduced that of fast-spiking GABAergic interneurons, suggesting a preferential action of 5-HT 1A agonists on 5-HT 1A receptors in fast-spiking GABA interneurons, particularly at lower doses (Lladó-Pelfort et al, 2012b).…”

Section: Role Of 5-ht Receptors On Cortical Neuron Activitymentioning

confidence: 99%

Serotonin modulation of cortical neurons and networks

Celada¹,

Puig²,

Artigas³

2013

Front. Integr. Neurosci.

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332

283

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The serotonergic pathways originating in the dorsal and median raphe nuclei (DR and MnR, respectively) are critically involved in cortical function. Serotonin (5-HT), acting on postsynaptic and presynaptic receptors, is involved in cognition, mood, impulse control and motor functions by (1) modulating the activity of different neuronal types, and (2) varying the release of other neurotransmitters, such as glutamate, GABA, acetylcholine and dopamine. Also, 5-HT seems to play an important role in cortical development. Of all cortical regions, the frontal lobe is the area most enriched in serotonergic axons and 5-HT receptors. 5-HT and selective receptor agonists modulate the excitability of cortical neurons and their discharge rate through the activation of several receptor subtypes, of which the 5-HT1A, 5-HT1B, 5-HT2A, and 5-HT3 subtypes play a major role. Little is known, however, on the role of other excitatory receptors moderately expressed in cortical areas, such as 5-HT2C, 5-HT4, 5-HT6, and 5-HT7. In vitro and in vivo studies suggest that 5-HT1A and 5-HT2A receptors are key players and exert opposite effects on the activity of pyramidal neurons in the medial prefrontal cortex (mPFC). The activation of 5-HT1A receptors in mPFC hyperpolarizes pyramidal neurons whereas that of 5-HT2A receptors results in neuronal depolarization, reduction of the afterhyperpolarization and increase of excitatory postsynaptic currents (EPSCs) and of discharge rate. 5-HT can also stimulate excitatory (5-HT2A and 5-HT3) and inhibitory (5-HT1A) receptors in GABA interneurons to modulate synaptic GABA inputs onto pyramidal neurons. Likewise, the pharmacological manipulation of various 5-HT receptors alters oscillatory activity in PFC, suggesting that 5-HT is also involved in the control of cortical network activity. A better understanding of the actions of 5-HT in PFC may help to develop treatments for mood and cognitive disorders associated with an abnormal function of the frontal lobe.

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In vivo electrophysiological and neurochemical effects of the selective 5-HT1A receptor agonist, F13640, at pre- and postsynaptic 5-HT1A receptors in the rat

Abstract: These results indicate that, upon systemic administration, F13640 activates both 5-HT(1A) autoreceptors and postsynaptic 5-HT(1A) receptors in prefrontal cortex with a similar potency. Both activities are likely involved in the analgesic properties of the compound.

Cited by 42 publications

References 61 publications

NLX-112, a novel 5-HT 1A receptor agonist for the treatment of l -DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat

NLX-112, a novel 5-HT 1A receptor agonist for the treatment of l -DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat

5‐Hydroxytryptamine_1A receptor‐activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation

Serotonin modulation of cortical neurons and networks

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In vivo electrophysiological and neurochemical effects of the selective 5-HT1A receptor agonist, F13640, at pre- and postsynaptic 5-HT1A receptors in the rat

Abstract: These results indicate that, upon systemic administration, F13640 activates both 5-HT(1A) autoreceptors and postsynaptic 5-HT(1A) receptors in prefrontal cortex with a similar potency. Both activities are likely involved in the analgesic properties of the compound.

Cited by 42 publications

References 61 publications

NLX-112, a novel 5-HT 1A receptor agonist for the treatment of l -DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat

NLX-112, a novel 5-HT 1A receptor agonist for the treatment of l -DOPA-induced dyskinesia: Behavioral and neurochemical profile in rat

5‐Hydroxytryptamine1A receptor‐activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation

Serotonin modulation of cortical neurons and networks

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Product

Resources

About

5‐Hydroxytryptamine_1A receptor‐activation hyperpolarizes pyramidal cells and suppresses hippocampal gamma oscillations via Kir3 channel activation