The alpha-7 receptor agonist EVP-6124 increases dopamine and glutamate efflux in rat medial prefrontal cortex and nucleus accumbens

Huang, Mei; Felix, Anna R.; Bhuvaneswaran, Chaya; Hilt, Dana; König, Gerhard; Meltzer, Herbert Y.

doi:10.1016/j.bcp.2011.07.044

Cited by 3 publications

(2 citation statements)

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“…Subsequent systemic treatment with subtype-specific cholinergic antagonists (scopolamine or MLA) was used to assess the contribution of mAChRs or α7 nAChRs to the observed effects. The applied doses of the two antagonists were chosen as typical intermediate doses within the physiologically and behaviorally relevant dose range for rodents, according to previous studies from our laboratory and elsewhere (Matsumoto et al, 2001 ; Pichat et al, 2007 ; Huang et al, 2011 ; Andriambeloson et al, 2014 ; Bali et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells

Bali

Nagy

Hernádi

2017

Front. Cell. Neurosci.

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The aim of the present study was to identify in vivo electrophysiological correlates of the interaction between cholinergic and glutamatergic neurotransmission underlying memory. Extracellular spike recordings were performed in the hippocampal CA1 region of anesthetized rats in combination with local microiontophoretic administration of N-methyl-D-aspartate (NMDA) and acetylcholine (ACh). Both NMDA and ACh increased the firing rate of the neurons. Furthermore, the simultaneous delivery of NMDA and ACh resulted in a more pronounced excitatory effect that was superadditive over the sum of the two mono-treatment effects and that was explained by cholinergic potentiation of glutamatergic neurotransmission. Next, animals were systemically treated with scopolamine or methyllycaconitine (MLA) to assess the contribution of muscarinic ACh receptor (mAChR) or α7 nicotinic ACh receptor (nAChR) receptor-mediated mechanisms to the observed effects. Scopolamine totally inhibited ACh-evoked firing, and attenuated the firing rate increase evoked by simultaneous application of NMDA and ACh. However, the superadditive nature of the combined effect was preserved. The α7 nAChR antagonist MLA robustly decreased the firing response to simultaneous application of NMDA and ACh, suspending their superadditive effect, without modifying the tonic firing rate increasing effect of ACh. These results provide the first in vivo electrophysiological evidence that, in the hippocampal CA1 region, α7 nAChRs contribute to pyramidal cell activity mainly through potentiation of glutamatergic signaling, while the direct cholinergic modulation of tonic firing is notably mediated by mAChRs. Furthermore, the present findings also reveal cellular physiological correlates of the interplay between cholinergic and glutamatergic agents in behavioral pharmacological models of cognitive decline.

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Section: Discussionmentioning

confidence: 99%

Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells

Bali

Nagy

Hernádi

2017

Front. Cell. Neurosci.

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“…EVP-6124 ((( R )-7-chloro- N -quinuclidin-3-yl)benzo[ b ] thiophene-2-carboxamide) is a representative quinuclidine amide analog developed by FORUM (formerly EnVivo) that acts as a potent partial agonist at α 7 nAChR (EC 50 =0.39 μmol/L, E max =42%) and an antagonist at 5-HT 3 receptors (IC 50 <10 nmol/L) 99 . It is also reported that EVP-6124 enhanced dopamine, acetylcholine, and glutamate efflux in the rat cortex and nucleus accumbens 131. , 132.…”

Section: α 7 Nachr Modulatorsmentioning

confidence: 95%

The current agonists and positive allosteric modulators of α 7 nAChR for CNS indications in clinical trials

Yang

Xiao

Sun

et al. 2017

Acta Pharmaceutica Sinica B

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The alpha-7 nicotinic acetylcholine receptor (α7 nAChR), consisting of homomeric α7 subunits, is a ligand-gated Ca2+-permeable ion channel implicated in cognition and neuropsychiatric disorders. Enhancement of α7 nAChR function is considered to be a potential therapeutic strategy aiming at ameliorating cognitive deficits of neuropsychiatric disorders such as Alzheimer's disease (AD) and schizophrenia. Currently, a number of α7 nAChR modulators have been reported and several of them have advanced into clinical trials. In this brief review, we outline recent progress made in understanding the role of the α7 nAChR in multiple neuropsychiatric disorders and the pharmacological effects of α7 nAChR modulators used in clinical trials.

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Nicotinic acetylcholine receptors: From basic science to therapeutics

Hurst

Rollema²,

Bertrand

2013

Pharmacology & Therapeutics

456

367

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The alpha-7 receptor agonist EVP-6124 increases dopamine and glutamate efflux in rat medial prefrontal cortex and nucleus accumbens

Cited by 3 publications

References 0 publications

Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells

Alpha7 Nicotinic Acetylcholine Receptors Play a Predominant Role in the Cholinergic Potentiation of N-Methyl-D-Aspartate Evoked Firing Responses of Hippocampal CA1 Pyramidal Cells

The current agonists and positive allosteric modulators of α 7 nAChR for CNS indications in clinical trials

Nicotinic acetylcholine receptors: From basic science to therapeutics

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