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S A Eaton - One of the best experts on this subject based on the ideXlab platform.
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Mediation of Thalamic Sensory Responses In Vivo by ACPD‐activated Excitatory Amino Acid Receptors
The European journal of neuroscience, 1993Co-Authors: S A Eaton, David C. Sunter, Peter M. Udvarhelyi, Jeffrey C. Watkins, E. F. Birse, B. Wharton, Thomas E. SaltAbstract:The existence of the so-called metabotropic excitatory Amino Acid Receptor has been known for some years. Various functions have been suggested for this Receptor, but the lack of selective antagonists for (IS, 3R)-Aminocyclopentane dicarboxylic Acid (ACPD) has precluded the direct demonstration of a functional role for this Receptor in synaptic processes. We describe here a specific antagonism of the excitatory responses of thalamic neurons to ACPD by two novel antagonists, and a parallel antagonism by these compounds of sensory synaptic responses to noxious stimuli of the same neurons. This provides the first direct pharmacological evidence for a functional role of ACPD-sensitive Receptors in central neurotransmission, and indicates that these Receptors may play an important part in central sensory processes.
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mediation of thalamic sensory responses in vivo by acpd activated excitatory Amino Acid Receptors
European Journal of Neuroscience, 1993Co-Authors: S A Eaton, David C. Sunter, Peter M. Udvarhelyi, Jeffrey C. Watkins, E. F. Birse, B. Wharton, T E SaltAbstract:The existence of the so-called metabotropic excitatory Amino Acid Receptor has been known for some years. Various functions have been suggested for this Receptor, but the lack of selective antagonists for (IS, 3R)-Aminocyclopentane dicarboxylic Acid (ACPD) has precluded the direct demonstration of a functional role for this Receptor in synaptic processes. We describe here a specific antagonism of the excitatory responses of thalamic neurons to ACPD by two novel antagonists, and a parallel antagonism by these compounds of sensory synaptic responses to noxious stimuli of the same neurons. This provides the first direct pharmacological evidence for a functional role of ACPD-sensitive Receptors in central neurotransmission, and indicates that these Receptors may play an important part in central sensory processes.
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excitatory actions of the metabotropic excitatory Amino Acid Receptor agonist trans 1 Amino cyclopentane 1 3 dicarboxylate t acpd on rat thalamic neurons in vivo
European Journal of Neuroscience, 1991Co-Authors: T E Salt, S A EatonAbstract:The metabotropic excitatory Amino Acid Receptor agonist trans-(+/-)-1-Amino-cyclopentane-1,3-dicarboxylate (t-ACPD) was applied to rat ventrobasal thalamic neurons by iontophoresis. This agonist typically evoked an excitatory response which was slower in onset and of longer duration than responses to the other excitatory Amino Acid agonists, N-methyl-aspartate, kainate or (R,S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate. Responses to t-ACPD were resistant to the excitatory Amino Acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione, 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic Acid and kynurenate. These results suggest that t-ACPD may exert its effects via the so-called 'metabotropic' excitatory Amino Acid Receptor. The putative antagonists at this Receptor, D-2-Amino-4-phosphono-butyrate (D-AP4), L-2-Amino-4-phosphono-butyrate (L-AP4) and L-2-Amino-3-phosphono-propionate (L-AP3), were able to reduce responses to t-ACPD under certain circumstances. However, such antagonism was always accompanied by similar reductions in excitatory responses to other agonists. These non-selective effects would appear to limit the usefulness of AP4 and AP3 as antagonists of t-ACPD.
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Excitatory Actions of the Metabotropic Excitatory Amino Acid Receptor Agonist, trans‐(±)‐1‐Amino‐cyclopentane‐1,3‐dicarboxylate (t‐ACPD), on Rat Thalamic Neurons In Vivo
The European journal of neuroscience, 1991Co-Authors: T E Salt, S A EatonAbstract:The metabotropic excitatory Amino Acid Receptor agonist trans-(+/-)-1-Amino-cyclopentane-1,3-dicarboxylate (t-ACPD) was applied to rat ventrobasal thalamic neurons by iontophoresis. This agonist typically evoked an excitatory response which was slower in onset and of longer duration than responses to the other excitatory Amino Acid agonists, N-methyl-aspartate, kainate or (R,S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate. Responses to t-ACPD were resistant to the excitatory Amino Acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione, 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic Acid and kynurenate. These results suggest that t-ACPD may exert its effects via the so-called 'metabotropic' excitatory Amino Acid Receptor. The putative antagonists at this Receptor, D-2-Amino-4-phosphono-butyrate (D-AP4), L-2-Amino-4-phosphono-butyrate (L-AP4) and L-2-Amino-3-phosphono-propionate (L-AP3), were able to reduce responses to t-ACPD under certain circumstances. However, such antagonism was always accompanied by similar reductions in excitatory responses to other agonists. These non-selective effects would appear to limit the usefulness of AP4 and AP3 as antagonists of t-ACPD.
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Sensory Excitatory Postsynaptic Potentials Mediated by NMDA and non-NMDA Receptors in the Thalamus in vivo
The European journal of neuroscience, 1991Co-Authors: Thomas E. Salt, S A EatonAbstract:Excitatory Amino Acid neurotransmitters, such as l-glutamate, act at several Receptors in the brain, which are sometimes referred to as N-methyl-d-aspartate (NMDA) and non-NMDA Receptors. Extensive in vitro work indicates that both NMDA Receptors and non-NMDA Receptors contribute to excitatory postsynaptic potentials (epsps). The contribution of NMDA Receptors to epsps in vivo under physiological conditions is, however, almost unknown. The Receptors that mediate the epsps evoked in thalamic relay cells by natural stimulation of sensory afferents have been investigated in anaesthetized rats, and we report the first pharmacological characterization of an excitatory Amino Acid Receptor-mediated epsp in vivo involving both non-NMDA Receptors and, in particular, NMDA Receptors.
T E Salt - One of the best experts on this subject based on the ideXlab platform.
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mediation of thalamic sensory responses in vivo by acpd activated excitatory Amino Acid Receptors
European Journal of Neuroscience, 1993Co-Authors: S A Eaton, David C. Sunter, Peter M. Udvarhelyi, Jeffrey C. Watkins, E. F. Birse, B. Wharton, T E SaltAbstract:The existence of the so-called metabotropic excitatory Amino Acid Receptor has been known for some years. Various functions have been suggested for this Receptor, but the lack of selective antagonists for (IS, 3R)-Aminocyclopentane dicarboxylic Acid (ACPD) has precluded the direct demonstration of a functional role for this Receptor in synaptic processes. We describe here a specific antagonism of the excitatory responses of thalamic neurons to ACPD by two novel antagonists, and a parallel antagonism by these compounds of sensory synaptic responses to noxious stimuli of the same neurons. This provides the first direct pharmacological evidence for a functional role of ACPD-sensitive Receptors in central neurotransmission, and indicates that these Receptors may play an important part in central sensory processes.
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excitatory actions of the metabotropic excitatory Amino Acid Receptor agonist trans 1 Amino cyclopentane 1 3 dicarboxylate t acpd on rat thalamic neurons in vivo
European Journal of Neuroscience, 1991Co-Authors: T E Salt, S A EatonAbstract:The metabotropic excitatory Amino Acid Receptor agonist trans-(+/-)-1-Amino-cyclopentane-1,3-dicarboxylate (t-ACPD) was applied to rat ventrobasal thalamic neurons by iontophoresis. This agonist typically evoked an excitatory response which was slower in onset and of longer duration than responses to the other excitatory Amino Acid agonists, N-methyl-aspartate, kainate or (R,S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate. Responses to t-ACPD were resistant to the excitatory Amino Acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione, 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic Acid and kynurenate. These results suggest that t-ACPD may exert its effects via the so-called 'metabotropic' excitatory Amino Acid Receptor. The putative antagonists at this Receptor, D-2-Amino-4-phosphono-butyrate (D-AP4), L-2-Amino-4-phosphono-butyrate (L-AP4) and L-2-Amino-3-phosphono-propionate (L-AP3), were able to reduce responses to t-ACPD under certain circumstances. However, such antagonism was always accompanied by similar reductions in excitatory responses to other agonists. These non-selective effects would appear to limit the usefulness of AP4 and AP3 as antagonists of t-ACPD.
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Excitatory Actions of the Metabotropic Excitatory Amino Acid Receptor Agonist, trans‐(±)‐1‐Amino‐cyclopentane‐1,3‐dicarboxylate (t‐ACPD), on Rat Thalamic Neurons In Vivo
The European journal of neuroscience, 1991Co-Authors: T E Salt, S A EatonAbstract:The metabotropic excitatory Amino Acid Receptor agonist trans-(+/-)-1-Amino-cyclopentane-1,3-dicarboxylate (t-ACPD) was applied to rat ventrobasal thalamic neurons by iontophoresis. This agonist typically evoked an excitatory response which was slower in onset and of longer duration than responses to the other excitatory Amino Acid agonists, N-methyl-aspartate, kainate or (R,S)-alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionate. Responses to t-ACPD were resistant to the excitatory Amino Acid antagonists 6-cyano-7-nitroquinoxaline-2,3-dione, 3-((RS)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic Acid and kynurenate. These results suggest that t-ACPD may exert its effects via the so-called 'metabotropic' excitatory Amino Acid Receptor. The putative antagonists at this Receptor, D-2-Amino-4-phosphono-butyrate (D-AP4), L-2-Amino-4-phosphono-butyrate (L-AP4) and L-2-Amino-3-phosphono-propionate (L-AP3), were able to reduce responses to t-ACPD under certain circumstances. However, such antagonism was always accompanied by similar reductions in excitatory responses to other agonists. These non-selective effects would appear to limit the usefulness of AP4 and AP3 as antagonists of t-ACPD.
Sylvie Puig - One of the best experts on this subject based on the ideXlab platform.
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neuronal model of tactile allodynia produced by spinal strychnine effects of excitatory Amino Acid Receptor antagonists and a μ opiate Receptor agonist
Pain, 1996Co-Authors: Linda S Sorkin, Sylvie PuigAbstract:Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA Receptor antagonists, but not by μ-opiate Receptor agonists. In this study, we sought to characterize the effect of focal glycine-Receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA Receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory Amino Acid Receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a μ-opiate Receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.
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Neuronal model of tactile allodynia produced by spinal strychnine: effects of excitatory Amino Acid Receptor antagonists and a mu-opiate Receptor agonist.
Pain, 1996Co-Authors: Linda S Sorkin, Sylvie PuigAbstract:Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA Receptor antagonists, but not by mu-opiate Receptor agonists. In this study, we sought to characterize the effect of focal glycine-Receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA Receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory Amino Acid Receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a mu-opiate Receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.
Linda S Sorkin - One of the best experts on this subject based on the ideXlab platform.
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neuronal model of tactile allodynia produced by spinal strychnine effects of excitatory Amino Acid Receptor antagonists and a μ opiate Receptor agonist
Pain, 1996Co-Authors: Linda S Sorkin, Sylvie PuigAbstract:Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA Receptor antagonists, but not by μ-opiate Receptor agonists. In this study, we sought to characterize the effect of focal glycine-Receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA Receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory Amino Acid Receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a μ-opiate Receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.
-
Neuronal model of tactile allodynia produced by spinal strychnine: effects of excitatory Amino Acid Receptor antagonists and a mu-opiate Receptor agonist.
Pain, 1996Co-Authors: Linda S Sorkin, Sylvie PuigAbstract:Touch evoked agitation (allodynia) can be induced by spinal delivery of strychnine and this effect is antagonized by intrathecal NMDA and non-NMDA Receptor antagonists, but not by mu-opiate Receptor agonists. In this study, we sought to characterize the effect of focal glycine-Receptor inhibition on spontaneous and evoked activity in dorsal horn neurons of the chloralose-anesthetized cat. Strychnine (1 mM) applied near the neurons through a dialysis fiber caused an enhanced response to hair deflection, enlargement of the low threshold receptive fields and in some cells, an increase in afterdischarge. These changes were observed only in cells that were activated by both hair deflection and high intensity mechanical stimulation. Subsequent co-administration of an NMDA Receptor antagonist (AP-7, 2.0 mM) preferentially blocked strychnine-associated effects without changing the original receptive field characteristics. Co-administration of a non-NMDA excitatory Amino Acid Receptor antagonist (CNQX, 1 mM) with the strychnine served to block low (brush) and high intensity (pinch) afferent input. In contrast, addition of a mu-opiate Receptor agonist (alfentanil 2.4 mM) to the strychnine perfusate selectively reduced responsiveness to high intensity stimulation, while having no effect on the exaggerated response to hair deflection. Given the functional and pharmacological similarity of the effects of spinal strychnine to post-nerve injury states in man, disinhibition due to a loss of glycinergic input may be associated with large myelinated fiber-mediated nociceptive states. Consistent with these data is the contention that under normal circumstances, afferent hair follicle input onto convergent neurons is regulated by a tonic glycinergic circuit. Removal of this regulatory influence leads to a magnification of low threshold tactile throughput in dorsal horn. This model may help to provide pharmacological insights into more efficacious treatments for such pain states that are relatively refractory to opioid therapies.
Thomas E. Salt - One of the best experts on this subject based on the ideXlab platform.
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Mediation of Thalamic Sensory Responses In Vivo by ACPD‐activated Excitatory Amino Acid Receptors
The European journal of neuroscience, 1993Co-Authors: S A Eaton, David C. Sunter, Peter M. Udvarhelyi, Jeffrey C. Watkins, E. F. Birse, B. Wharton, Thomas E. SaltAbstract:The existence of the so-called metabotropic excitatory Amino Acid Receptor has been known for some years. Various functions have been suggested for this Receptor, but the lack of selective antagonists for (IS, 3R)-Aminocyclopentane dicarboxylic Acid (ACPD) has precluded the direct demonstration of a functional role for this Receptor in synaptic processes. We describe here a specific antagonism of the excitatory responses of thalamic neurons to ACPD by two novel antagonists, and a parallel antagonism by these compounds of sensory synaptic responses to noxious stimuli of the same neurons. This provides the first direct pharmacological evidence for a functional role of ACPD-sensitive Receptors in central neurotransmission, and indicates that these Receptors may play an important part in central sensory processes.
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Sensory Excitatory Postsynaptic Potentials Mediated by NMDA and non-NMDA Receptors in the Thalamus in vivo
The European journal of neuroscience, 1991Co-Authors: Thomas E. Salt, S A EatonAbstract:Excitatory Amino Acid neurotransmitters, such as l-glutamate, act at several Receptors in the brain, which are sometimes referred to as N-methyl-d-aspartate (NMDA) and non-NMDA Receptors. Extensive in vitro work indicates that both NMDA Receptors and non-NMDA Receptors contribute to excitatory postsynaptic potentials (epsps). The contribution of NMDA Receptors to epsps in vivo under physiological conditions is, however, almost unknown. The Receptors that mediate the epsps evoked in thalamic relay cells by natural stimulation of sensory afferents have been investigated in anaesthetized rats, and we report the first pharmacological characterization of an excitatory Amino Acid Receptor-mediated epsp in vivo involving both non-NMDA Receptors and, in particular, NMDA Receptors.