The Experts below are selected from a list of 276 Experts worldwide ranked by ideXlab platform
Michael W. Decker - One of the best experts on this subject based on the ideXlab platform.
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Effect of intraventricular injections of Dihydro-Beta-Erythroidine (DH,β E) on spatial memory in the rat
Brain Research, 1996Co-Authors: Peter Curzon, Jorge D. Brioni, Michael W. DeckerAbstract:Abstract The analysis of the behavioral effect of the nicotinic acetylcholine receptor (nAChR) antagonists has been generally based on drugs which act at the associated ion channel. In contrast Dihydro-Beta-Erythroidine (DH,β E) is a competitive antagonist at the nAChR. Using rats, DH,β E was injected intraventricularly prior to training in two spatial tests, the Morns Water Maze and a Win-Stay radial maze. In addition DH,β E 300 nmol was used to reverse the effect of (−)-nicotine on locomotor activity. In the Moms Water Maze DH,β E (300 nmol) disrupted memory of the platform location as measured by crosses of the area in a probe trial. At 300 nmol DH,β E showed no sensorimotor effects in a visible platform test. In the Win-Stay task there was a significant, dose dependent disruption of spatial memory. A dissociation of nicotine's effects on locomotor activity was observed, in that DH,β E 300 nmol was able to significantly attenuate (−)-nicotine enhancement of horizontal motor activity, but did not affect the initial reduction of vertical activity. Nicotinic processing of memory appears to be involved in these tests of spatial memory.
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Erysodine, a competitive antagonist at neuronal nicotinic acetylcholine receptors.
European journal of pharmacology, 1995Co-Authors: Michael W. Decker, David J. Anderson, Jorge D. Brioni, Diana L. Donnelly-roberts, Chae Hee Kang, Alyssa B. O'neill, Marietta Piattoni-kaplan, Susan Swanson, James P. SullivanAbstract:Erysodine, an erythrina alkaloid related to Dihydro-Beta-Erythroidine, was found to be a more potent inhibitor of [3H]cytisine binding at neuronal nicotinic acetylcholine receptors but a less potent inhibitor of [125I]alpha-bungarotoxin binding at muscle-type nicotinic acetylcholine receptors than Dihydro-Beta-Erythroidine. Erysodine was a competitive, reversible antagonist of (-)-nicotine-induced dopamine release from striatal slices and inhibited (-)-nicotine-induced 86Rb+ efflux from IMR-32 cells. Erysodine was equipotent with Dihydro-Beta-Erythroidine in the dopamine release assay but 10-fold more potent in the 86Rb+ efflux assay, suggesting differential subtype selectivity for these two antagonists. Erysodine, systemically administered to mice, entered the brain and significantly attentuated nicotine's hypothermic effects and its anxiolytic-like effects in the elevated plus-maze test. There was greater separation between antagonist and toxic doses for erysodine than for Dihydro-Beta-Erythroidine, perhaps because of erysodine's greater selectivity for neuronal receptors. In rats, erysodine prevented both the early developing decrease and the late-developing increase in locomotor activity produced by (-)-nicotine. The potent and competitive nature of erysodine's antagonism together with its ability to enter the brain after systemic administration suggest that erysodine may be a useful tool in characterizing neuronal nicotinic acetylcholine receptors.
Norio Sakai - One of the best experts on this subject based on the ideXlab platform.
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Postsynaptic alpha 4 Beta 2 and alpha 7 type nicotinic acetylcholine receptors contribute to the local and endogenous acetylcholine-mediated synaptic transmissions in nigral dopaminergic neurons.
Brain research, 2004Co-Authors: Hiroaki Matsubayashi, Taku Amano, Takahiro Seki, Masashi Sasa, Norio SakaiAbstract:The local and endogenous nicotinic neuronal transmissions of dopaminergic neurons in the substantia nigra were confirmed electrophysiologically using a slice-patch technique. After identifying dopaminergic neurons based on their electrophysiological characteristics, miniature postsynaptic inward currents were recorded in the presence of atropine (a muscarinic acetylcholine receptor antagonist), bicuculline (a GABA receptor antagonist) and L-glutamic acid diethyl ester (GDEE) (a non-selective glutamate receptor antagonist). Under conditions that eliminated muscarinic, GABAergic and glutamatergic synaptic transmissions, we found miniature currents that were inhibited by the specific neuronal nicotinic receptor antagonists, Dihydro-Beta-Erythroidine (DHBetaE) and/or methyllycaconitine (MLA) (selective alpha4Beta2 and/or alpha7 nicotinic acetylcholine receptor antagonists, respectively). Under the same extracellular conditions, local stimulations in the vicinity of a target neuron evoked excitatory postsynaptic inward currents (EPSCs). These EPSCs were elicited in an extracellular Ca(2+) dependent manner and were also blocked by DHBetaE and/or MLA. These results suggest that dopaminergic neurons in the substantia nigra receive excitatory cholinergic inputs that are mediated via at least two types of postsynaptic nicotinic receptors, namely alpha7 and alpha4Beta2 subtypes.
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Postsynaptic α4β2 and α7 type nicotinic acetylcholine receptors contribute to the local and endogenous acetylcholine-mediated synaptic transmissions in nigral dopaminergic neurons
Brain Research, 2004Co-Authors: Hiroaki Matsubayashi, Taku Amano, Takahiro Seki, Masashi Sasa, Norio SakaiAbstract:The local and endogenous nicotinic neuronal transmissions of dopaminergic neurons in the substantia nigra were confirmed electrophysiologically using a slice-patch technique. After identifying dopaminergic neurons based on their electrophysiological characteristics, miniature postsynaptic inward currents were recorded in the presence of atropine (a muscarinic acetylcholine receptor antagonist), bicuculline (a GABA receptor antagonist) and L-glutamic acid diethyl ester (GDEE) (a non-selective glutamate receptor antagonist). Under conditions that eliminated muscarinic, GABAergic and glutamatergic synaptic transmissions, we found miniature currents that were inhibited by the specific neuronal nicotinic receptor antagonists, Dihydro-Beta-Erythroidine (DHBetaE) and/or methyllycaconitine (MLA) (selective alpha4Beta2 and/or alpha7 nicotinic acetylcholine receptor antagonists, respectively). Under the same extracellular conditions, local stimulations in the vicinity of a target neuron evoked excitatory postsynaptic inward currents (EPSCs). These EPSCs were elicited in an extracellular Ca(2+) dependent manner and were also blocked by DHBetaE and/or MLA. These results suggest that dopaminergic neurons in the substantia nigra receive excitatory cholinergic inputs that are mediated via at least two types of postsynaptic nicotinic receptors, namely alpha7 and alpha4Beta2 subtypes.
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Electrophysiological characterization of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra.
Journal of pharmacological sciences, 2003Co-Authors: Hiroaki Matsubayashi, Taku Amano, Takahiro Seki, Masashi Sasa, Norio SakaiAbstract:The electrophysiological characteristics of nicotine-induced excitation of dopaminergic neurons in the rat substantia nigra was investigated using the whole-cell patch clamp technique under the voltage-clamp mode. Nicotine (0.01 - 100 microM) induced inward currents corresponding to nicotine-induced depolarization with an increase in firing in a dose-dependent manner. This current was inhibited by Dihydro-Beta-Erythroidine, a selective antagonist for the alpha4Beta2 type neuronal nicotinic receptor. Nicotine directly acts on postsynaptic alpha4Beta2 type nicotinic receptors and induces inward currents, resulting in excitation of dopaminergic neurons in the substantia nigra and subsequent enhancement of dopamine release in the corpus striatum.
Jean-pierre Changeux - One of the best experts on this subject based on the ideXlab platform.
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Inhibition of both alpha7* and Beta2* nicotinic acetylcholine receptors is necessary to prevent development of sensitization to cocaine-elicited increases in extracellular dopamine levels in the ventral striatum.
Psychopharmacology, 2006Co-Authors: Lara Zanetti, Jean-pierre Changeux, Alban De Kerchove D'exaerde, Alessio Zanardi, Marina R. Picciotto, Michele ZoliAbstract:RATIONALE: Several studies have suggested that nicotine treatment can modulate the behavioral and neurochemical responses to other psychostimulants, such as cocaine. OBJECTIVES: The current study examined the hypothesis that nicotinic acetylcholine receptor (nAChR) blockade influences the ability of cocaine to elicit increases in extracellular dopamine levels. MATERIALS AND METHODS: Pharmacological studies using nicotinic antagonists as well as genetic inactivation of Beta2* nAChRs were used to determine the effect of nAChR blockade on dopamine levels in ventral striatum elicited by acute or repeated administrations of cocaine in mice. RESULTS: Administration of mecamylamine (a general nicotinic antagonist that is not highly selective for individual nAChR subtypes) or co-administration of methyllycaconitine (a more selective antagonist of alpha7* nAChRs) with Dihydro-Beta-Erythroidine (a more selective antagonist of Beta2* nAChRs and other heteromeric nAChR subtypes) prevented sensitization of cocaine-elicited increases in extracellular DA levels in the ventral striatum in wild-type mice. In contrast, neither of the more specific antagonists alone was effective in preventing sensitization. Finally, methyllycaconitine administration prevents sensitization in Beta2-/- mice but not in Beta2+/+ or wild-type mice. CONCLUSIONS: These data indicate that inhibition of both alpha7* and Beta2* nAChRs is necessary to prevent development of sensitization of cocaine-elicited increases in extracellular dopamine levels in the ventral striatum of mice.
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Neurotoxicity of channel mutations in heterologously expressed α7‐nicotinic acetylcholine receptors
The European journal of neuroscience, 2001Co-Authors: Ronald J. Lukas, Jean-pierre Changeux, Bruno Buisson, Linda Lucero, Jean Luc Galzi, Elzbieta Puchacz, John D. Fryer, Daniel BertrandAbstract:Nicotinic acetylcholine receptors (nAChR) composed of chick alpha7 subunits mutated to threonine at amino acid valine-251 in the putative channel-lining M2 domain were expressed heterologously in several neuron-like and non-neuronal mammalian cell lines. Expression of mutant alpha7-nAChR is toxic to neuron-like cells of the human neuroblastoma cell lines SH-SY5Y and IMR-32, but not to several other cell types. Growth in the presence of the alpha7-nAChR antagonist methyllycaconitine (MLA) protects against neurotoxicity, as does gradual downregulation of functional, mutant alpha7-nAChR in surviving transfected SH-SY5Y cells. Relative to wild-type alpha7-nAChR, functional alpha7-nAChR mutants show a higher affinity for agonists, slower rates of desensitization, and sensitivity to Dihydro-Beta-Erythroidine (DHBetaE) as an agonist, but they retain sensitivity to MLA as a competitive antagonist. These findings demonstrate that expression of hyperfunctional, mutant forms of Ca2+-permeable alpha7-nAChR is toxic to neuron-like cells.
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molecular and physiological diversity of nicotinic acetylcholine receptors in the midbrain dopaminergic nuclei
The Journal of Neuroscience, 2001Co-Authors: Ruby Klink, Alban De Kerchove Dexaerde, Michele Zoli, Jean-pierre ChangeuxAbstract:Nicotinic acetylcholine receptors (nAChRs) on dopaminergic (DA) and GABAergic (Gaba) projection neurons of the substantia nigra (SN) and ventral tegmental area (VTA) are characterized by single-cell RT-PCR and patch-clamp recordings in slices of rat and wild-type, Beta2-/-, alpha4-/-, and alpha7-/- mice. The eight nAChR subunits expressed in these nuclei, alpha3-7 and Beta2-4, contribute to four different types of nAChR-mediated currents. Most DA neurons in the SN and VTA express two nAChR subtypes. One is inhibited by Dihydro-Beta-Erythroidine (2 microm), alpha-conotoxin MII (10 nm), and methyllycaconitine (1 nm) but does not contain the alpha7 subunit; it possesses a putative alpha4alpha6alpha5(Beta2)(2) composition. The other subtype is inhibited by Dihydro-Beta-Erythroidine (2 microm) and has a putative alpha4alpha5(Beta2)(2) composition. Gaba neurons in the VTA exhibit a third subtype with a putative (alpha4)(2)(Beta2)(3) composition, whereas Gaba neurons in the SN have either the putative (alpha4)(2)(Beta2)(3) oligomer or the putative alpha4alpha6alpha5(Beta2)(2) oligomer. The fourth subtype, a putative (alpha7)(5) homomer, is encountered in less than half of DA and Gaba neurons, in the SN as well as in the VTA. Neurons in the DA nuclei thus exhibit a diversity of nAChRs that might differentially modulate reinforcement and motor behavior.
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Paradoxical allosteric effects of competitive inhibitors on neuronal alpha7 nicotinic receptor mutants
NeuroReport, 1997Co-Authors: Sonia Bertrand, Jean-pierre Changeux, P.j. Corringer, Anne Devillers-thiéry, Eleonora Palma, Bruno Buisson, Stuart Edelstein, Daniel BertrandAbstract:Mutation of the conserved leucine residue, in the second transmembrane domain of the neuronal alpha7 acetylcholine receptor to a threonine (L247T) causes pleiotropic alterations of receptor properties. In this study we examined the effects of competitive inhibitors on the alpha7-L247T physiological responses. While the alpha7 competitive inhibitor Dihydro-Beta-Erythroidine evoked a current comparable to that induced by ACh, other inhibitors such as methyllycaconitine (MLA) and alpha-bungarotoxin (alpha-Bgt) caused a blockade of alpha7-L247T to ACh activation. When applied in the absence of ACh, MLA or alpha-Bgt reduced the cell leakage current, showing that alpha7-L247T displays a significant fraction (10%) of spontaneously open channels. These data can be interpreted in terms of an allosteric model, assuming that the L247T mutant possesses a low isomerization constant L and that MLA and alpha-Bgt stabilize the closed, resting state.
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Paradoxical allosteric effects of competitive inhibitors on neuronal α7 nicotinic receptor mutants
Neuroreport, 1997Co-Authors: Sonia Bertrand, Jean-pierre Changeux, P.j. Corringer, Anne Devillers-thiéry, Eleonora Palma, Bruno Buisson, Stuart J. Edelstein, Daniel BertrandAbstract:Mutation of the conserved leucine residue, in the second transmembrane domain of the neuronal alpha7 acetylcholine receptor to a threonine (L247T) causes pleiotropic alterations of receptor properties. In this study we examined the effects of competitive inhibitors on the alpha7-L247T physiological responses. While the alpha7 competitive inhibitor Dihydro-Beta-Erythroidine evoked a current comparable to that induced by ACh, other inhibitors such as methyllycaconitine (MLA) and alpha-bungarotoxin (alpha-Bgt) caused a blockade of alpha7-L247T to ACh activation. When applied in the absence of ACh, MLA or alpha-Bgt reduced the cell leakage current, showing that alpha7-L247T displays a significant fraction (10%) of spontaneously open channels. These data can be interpreted in terms of an allosteric model, assuming that the L247T mutant possesses a low isomerization constant L and that MLA and alpha-Bgt stabilize the closed, resting state.
Peter Curzon - One of the best experts on this subject based on the ideXlab platform.
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Effect of intraventricular injections of Dihydro-Beta-Erythroidine (DH,β E) on spatial memory in the rat
Brain Research, 1996Co-Authors: Peter Curzon, Jorge D. Brioni, Michael W. DeckerAbstract:Abstract The analysis of the behavioral effect of the nicotinic acetylcholine receptor (nAChR) antagonists has been generally based on drugs which act at the associated ion channel. In contrast Dihydro-Beta-Erythroidine (DH,β E) is a competitive antagonist at the nAChR. Using rats, DH,β E was injected intraventricularly prior to training in two spatial tests, the Morns Water Maze and a Win-Stay radial maze. In addition DH,β E 300 nmol was used to reverse the effect of (−)-nicotine on locomotor activity. In the Moms Water Maze DH,β E (300 nmol) disrupted memory of the platform location as measured by crosses of the area in a probe trial. At 300 nmol DH,β E showed no sensorimotor effects in a visible platform test. In the Win-Stay task there was a significant, dose dependent disruption of spatial memory. A dissociation of nicotine's effects on locomotor activity was observed, in that DH,β E 300 nmol was able to significantly attenuate (−)-nicotine enhancement of horizontal motor activity, but did not affect the initial reduction of vertical activity. Nicotinic processing of memory appears to be involved in these tests of spatial memory.
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Effect of intraventricular injections of Dihydro-Beta-Erythroidine (DH Beta E) on spatial memory in the rat.
Brain research, 1996Co-Authors: Peter Curzon, J D Brioni, M W DeckerAbstract:The analysis of the behavioral effect of the nicotinic acetylcholine receptor (nAChR) antagonists has been generally based on drugs which act at the associated ion channel. In contrast Dihydro-Beta-Erythroidine (DH Beta E) is a competitive antagonist at the nAChR. Using rats, DH Beta E was injected intraventricularly prior to training in two spatial tests, the Morris Water Maze and a Win-Stay radial maze. In addition DH Beta E 300 nmol was used to reverse the effect of (-)-nicotine on locomotor activity. In the Morris Water Maze DH Beta E (300 nmol) disrupted memory of the platform location as measured by crosses of the area in a probe trial. At 300 nmol DH Beta E showed no sensorimotor effects in a visible platform test. In the Win-Stay task there was a significant, dose dependent disruption of spatial memory. A dissociation of nicotine's effects on locomotor activity was observed, in that DH Beta E 300 nmol was able to significantly attenuate (-)-nicotine enhancement of horizontal motor activity, but did not affect the initial reduction of vertical activity. Nicotinic processing of memory appears to be involved in these tests of spatial memory.
M W Decker - One of the best experts on this subject based on the ideXlab platform.
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Effect of intraventricular injections of Dihydro-Beta-Erythroidine (DH Beta E) on spatial memory in the rat.
Brain research, 1996Co-Authors: Peter Curzon, J D Brioni, M W DeckerAbstract:The analysis of the behavioral effect of the nicotinic acetylcholine receptor (nAChR) antagonists has been generally based on drugs which act at the associated ion channel. In contrast Dihydro-Beta-Erythroidine (DH Beta E) is a competitive antagonist at the nAChR. Using rats, DH Beta E was injected intraventricularly prior to training in two spatial tests, the Morris Water Maze and a Win-Stay radial maze. In addition DH Beta E 300 nmol was used to reverse the effect of (-)-nicotine on locomotor activity. In the Morris Water Maze DH Beta E (300 nmol) disrupted memory of the platform location as measured by crosses of the area in a probe trial. At 300 nmol DH Beta E showed no sensorimotor effects in a visible platform test. In the Win-Stay task there was a significant, dose dependent disruption of spatial memory. A dissociation of nicotine's effects on locomotor activity was observed, in that DH Beta E 300 nmol was able to significantly attenuate (-)-nicotine enhancement of horizontal motor activity, but did not affect the initial reduction of vertical activity. Nicotinic processing of memory appears to be involved in these tests of spatial memory.