Search PubMed⌕ Search

Biomedical subjects

T E Salt

Publications and source records attributed to T E Salt.

At least 91 records · Page 5Linked to original sources
PubMed1983

Pharmacological differentiation between responses of rat medullary dorsal horn neurons to noxious mechanical and noxious thermal cutaneous stimuli.

Response of lamina V medullary dorsal horn neurons to noxious thermal and noxious mechanical facial stimuli were challenged with iontophoretically applied cis-2,3-piperidine dicarboxylic acid, a broad spectrum excitatory amino acid antagonist. This antagonist reduced neuronal responses to noxious mechanical stimuli but not responses to noxious thermal stimuli. These results suggest that different neural mechanisms underlie the responses of lamina V neurons to different noxious stimuli, and that responses to noxious mechanical stimuli appear to involve excitatory amino acid receptors.

Animals↗
PubMed1983

Excitation of single sensory neurones in the rat caudal trigeminal nucleus by iontophoretically applied adenosine 5'-triphosphate.

ATP can be released from the peripheral endings of sensory nerves, and thus may be a neurotransmitter of primary afferent fibres [12]. We have found that ATP is excitatory when applied to single sensory neurones in the rat caudal trigeminal nucleus, and this action is consistent with a neurotransmitter role. However, adenosine monophosphate and pyrophosphate, two metabolites of ATP, were respectively found to be inhibitory and excitatory, and thus it remains unclear whether the actions of ATP are direct or are due to actions of its metabolites.

Adenosine Triphosphate↗
PubMed1983

The behavioural effects of intrathecally administered [D-PRO2, D-TRP7,9]-substance P, an analogue with presumed antagonist actions, in the rat.

[D-Pro2, D-Trp7,9]-substance P, an analogue of the putative nociceptive primary afferent neurotransmitter substance P, was administered to rats via chronically implanted intrathecal catheters (0.5-2.5 nmol per rat). Several animals showed large elevations of thermal and mechanical nociceptive thresholds, but these effects were always accompanied by profound, often long-lasting, impairments of motor function and thus cannot be regarded as a specific antinociceptive effect of the drug. These behavioural effects are considered to be probably due to direct spinal actions of the drug rather than antagonism of spinal substance P systems.

Analgesics↗
PubMed1983

Effects of excitatory amino acids and their antagonists on membrane and action potentials of cat caudate neurones.

The electrical activity of caudate neurones was recorded with intracellular electrodes in halothane anaesthetized cats. Agonists and antagonists of excitatory amino acid receptors were applied by micro-ionophoresis and their effects on membrane- and action potentials and on cortically evoked synaptic potentials evaluated. The agonists, L-aspartate (asp), L-glutamate (glu), N-methyl-DL-aspartate (NMA), quinolinate and quisqualate all depolarized the membrane, caused repetitive firing, reduced the apparent amplitude of the cortically evoked excitatory post-synaptic potentials (e.p.s.p.s) and increased the amplitude of the associated inhibitory post-synaptic potential. Two of the agonists, NMA and quinolinate, additionally caused the appearance of up to 500 ms long depolarizations (plateaus) on the falling phase of action potentials. These plateaus were seen in about two-thirds of the cells in this sample while in the other third the excitatory effects of NMA and quinolinate were indistinguishable from those of glu and quisqualate. The N-methyl-D-aspartate (NMDA) receptor antagonist D-alpha-aminoadipate (DAA) reversibly inhibited the effects of NMA and quinolinate but only on those cells where these two agents evoked action potential plateaus while on the same cells the effects of asp, glu and quisqualate were either only weakly antagonized or not affected. On cells not displaying plateaus to NMA or quinolinate none of the effects of the agonists could be antagonized by DAA. DAA applications that completely antagonized the effects of NMA never reduced the amplitudes of cortically evoked e.p.s.p.s. Cis-2,3-piperidine dicarboxylate also blocked the effects of NMA and asp at low application currents while at higher currents it enhanced the effects of glu or asp although still retaining its NMA antagonistic activity. High-frequency stimulation of the cortico-caudate pathway resulted in long-lasting depolarizations and repetitive firing, but plateaus of the type caused by NMA or quinolinate were not seen.

2-Aminoadipic Acid↗
PubMed1982

Evaluation of (D-Pro2, D-Trp7,9)-substance P as an antagonist of substance P responses in the rat central nervous system.

The (D-Pro2, D-Trp7,9) analogue of substance P has been tested for substance P antagonist activity in the caudal trigeminal nucleus in vivo, and in the isolated spinal cord in vitro. In neither case was the analogue found to be a specific antagonist of substance P, although the analogue did have weak antagonist actions in the isolated guinea-pig ileum preparation. It is concluded that the analogue is not a suitable tool for the identification of putative substance P systems in the spinal cord or the caudal trigeminal nucleus of the rat.

Animals↗
PubMed1982

Differentiation of excitatory amino acid receptors in the rat caudal trigeminal nucleus: a microiontophoretic study.

The excitatory amino acid antagonist, D-alpha-aminoadipate, was found to be a potent antagonist of responses to N-methyl-D-aspartate and L-aspartate, but less potent against L-glutamate responses of neurones in the rat caudal trigeminal nucleus. The responses to quisqualate and kainate were relatively unaffected by D-alpha-aminoadipate, but were antagonized by the two antagonists cis-2,3-piperidine dicarboxylate and gamma-D-glutamylglycine. These two antagonists had effectively similar spectra of activity. It is concluded that there is a distinct N-methyl-D-aspartate receptor in the trigeminal nucleus caudalis, and that kainate and quisqualate may act on a different, but common, receptor. Exogenously applied L-glutamate appears to act at both of these receptors, but exogenously applied L-aspartate appears to act almost exclusively on a D-alpha-aminoadipate sensitive site that may be the N-methyl-D-aspartate receptor. The kainate/quisqualate receptor is thought to be involved in the synaptic excitation of neurones in the caudal trigeminal nucleus by non-noxious mechanical stimuli.

2-Aminoadipic Acid↗
PubMed1982

The effects of capsaicin pre-treatment on the responses of single neurones to sensory stimuli in the trigeminal nucleus caudalis of the rat: evidence against a role for substance P as the neurotransmitter serving thermal nociception.

Rats were systemically pre-treated with capsaicin either on the first day of life or at an age of 1 month. Both treatments were found to deplete substance P levels in the trigeminal nucleus caudalis (55.6% and 57.9% depletions, respectively). Extracellular single neurone recordings in the trigeminal nucleus caudalis revealed that neither type of capsaicin treatment greatly altered the proportions of neurones responding to non-noxious or noxious mechanical stimulation of the face. However, the proportion of mechanically-nociceptive neurones also responding to noxious thermal stimulation was greatly reduced in neonatally-treated, but not adult-treated rats. As both methods of capsaicin treatment caused similar depletions of substance P, it is concluded that this peptide may not be the neurotransmitter of afferent fibres to the trigeminal nucleus caudalis signalling thermal nociception.

Animals↗
PubMed1982

An ionophoretic study of the responses of rat caudal trigeminal nucleus neurones to non-noxious mechanical sensory stimuli.

1. Extracellular recordings of the responses of single caudal trigeminal nucleus neurones to non-noxious and noxious facial stimuli and to ionophoretically applied L-glutamate, L-aspartate and acetylcholine were made in urethane anaesthetized rats. 2. Neurones excited by non-noxious mechanical stimuli were located primarily in the magnocellular part of nucleus caudalis, whereas neurones excited by both noxious and non-noxious stimuli were located either ventromedially to the magnocellular part of nucleus caudalis or superficially to the substantia gelatinosa. 3. Both L-aspartate and L-glutamate were found to excite all neurones tested in nucleus caudalis. In contrast, however, acetylcholine was found to excite only 31% of the neurones tested. 4. Responses of nucleus caudalis neurones to non-noxious sensory stimulation were not antagonized by the excitatory amino acid antagonist D-alpha-aminoadipate, but were antagonized by cis-2, 3-piperidine dicarboxylate and gamma-D-glutamylglycine, two excitatory amino acid antagonists with a broader spectrum of action. 5. It is concluded that the chemical synaptic transmitter of non-nociceptive mechanoreceptive primary afferent fibres to nucleus caudalis may be a ligand for an excitatory amino acid receptor other than a D-alpha-aminoadipate-sensitive receptor. The synaptic receptor may thus be of the kainate or quisqualate type, and the transmitter possibly L-glutamate, L-aspartate or an as yet unidentified substance.

Acetylcholine↗
PubMed1981

Excitatory amino acids as transmitter candidates of vibrissae afferent fibres to the rat trigeminal nucleus caudalis.

Responses of single neurones to vibrissal stimulation and to the iontophoretically applied putative neurotransmitters, L-glutamate and L-aspartate, were recorded in the trigeminal nucleus caudalis of the rat. Vibrissal responses were unaffected by the specific N-methyl-D-aspartate receptor antagonist, D-alpha-aminoadipate, but were antagonized by the broad-spectrum amino acid antagonist cis-2,3-piperidine dicarboxylate. These findings suggest that the neurotransmitter of vibrissae afferent fibres may be an endogenous excitatory amino acid acting at a receptor other than the N-methyl-D-aspartate receptor.

Action Potentials↗
PubMed1980

The effects of microiontophoretically applied capsaicin and substance P on single neurones in the rat and cat brain.

Microiontophoretically applied capsaicin (10-480 nA) excited neurones in trigeminal nucleus caudalis (ntV) or potentiated their amino acid-induced excitation (20 of 23 neurones); inhibited one neurone; and had no effect on 2 neurones. Substance P (SP) excited 8 of 9 ntV neurones, and of these 8 neurones 6 were excited, one was depressed, and one was unaffected by capsaicin. Of 13 cerebellar neurones, 5 were depressed by capsaicin and 8 were unaffected. SP excited 3 of 5 cerebellar neurones. It is concluded that the excitatory action of capsaicin in ntV may be due to release of SP from neuronal structures and that the lack of excitatory effects seen in the cerebellum may reflect the absence of SP-containing neurones in this structure.

Action Potentials↗
PubMed1980

Actions of microiontophoretically applied oxytocin, and immunohistochemical localization of oxytocin, vasopressin and neurophysin in the rat caudal medulla.

Oxytocin-, vasopressin- and neurophysin-containing axons were visualized within the rat caudal medulla using the immunoperoxidase technique. The highest densities of axons and terminals were found in the nucleus tractus solitarius, nucleus dorsalis vagus, nucleus commissuralis, nucleus reticularis lateralis and within the marginal layer of the nucleus trigeminalis. In these areas, oxytocin fibres predominated markedly over vasopressin fibres. In a series of electrophysiological experiments, neurones in these and surrounding areas were predominantly depressed following the iontophoretic application of oxytocin. This depression was seen on both spontaneous and glutamate-evoked neuronal firing.

Action Potentials↗
PubMedDate not supplied

A comparison of the effectiveness of intravenous morphine at attenuating the nociceptive responses of medullary dorsal horn and thalamic neurones.

In anaesthetized rats microelectrode recordings were made of single neurone activity in the medullary dorsal horn and in the thalamus. Ratemeter records were made of responses evoked by peripheral noxious stimuli. When consistent control responses had been obtained, morphine sulphate was administered by intravenous injection, and the total dose necessary to abolish or maximally attenuate nociceptive responses was recorded. For thalamic responses a mean dose of 0.7 +/- 0.18 mg/kg (mean +/- SEM, n = 16) was obtained, whereas for attenuation of medullary dorsal horn responses a mean dose of 2.5 +/- 0.72 mg/kg (mean +/- SEM, n = 13) was required. The greater sensitivity of the thalamic responses suggests that the effect of morphine at this site is not merely a consequence of a spinal action of the opiate and that an important component of the antinociceptive action is supraspinal.

Animals↗
PubMedDate not supplied

Excitatory amino acid receptors modulate habituation of the response to visual stimulation in the cat superior colliculus.

In visual neurones of the superficial layers of the superior colliculus (SSC), repetitive stimulation causes a progressive decline in the size of the response to the stimulus, usually known as response habituation or response adaptation. A mechanism has been proposed in which habituation results from coactivation of excitatory and inhibitory neurones, and the responses of the inhibitory neurones block the response to subsequent stimulus presentations. Excitatory amino acid (EAA) neurotransmitters mediate visual responses via NMDA and non-NMDA receptors in cat SSC. We have investigated the role of these receptors in the generation of response habituation. Following the iontophoretic application of the EAA antagonists CNQX, AP5 or CPP, repetitive visual stimulation paradigms which normally produce response habituation no longer do so. Indeed the response to each presentation of the stimulus is similar. Intravenous administration of the dissociative anesthetic ketamine (2-10 mg/kg) had similar actions to iontophoretically applied NMDA antagonists. The data imply that intracollicular mechanisms activated by NMDA and non-NMDA receptors contribute to the generation of the inhibitory responses in SCC which lead to response habituation. Furthermore, the effects seen with ketamine anesthesia suggest that the use of ketamine in studies of sensory systems may result in the lack of habituation.

Animals↗
PubMedDate not supplied

Corticofugal influences on visual responses in cat superior colliculus: the role of NMDA receptors.

The role of N-methyl-D-aspartate (NMDA) receptors in the mediation of cortical inputs to visual neurones in the superficial layers of the superior colliculus (SSC) has been investigated. Extracellular recording with iontophoresis in the SSC of cortically intact cats has demonstrated that visual responses of most neurones were reduced by iontophoretic application of the NMDA receptor antagonist D-2-amino-5-phosphonopentanoate (AP5). Following inactivation of areas 17 and 18 of the visual cortex with topical lignocaine, the visual responses of 11, previously AP5-sensitive, neurones were no longer reduced by AP5 ejection. The cortical input is generally assumed to influence the directional responses of visual neurones in SSC. However, detailed study of the directional bias showed that the degree of directional tuning in SSC neurones was similar to that of retinal ganglion cells, as previously described by others. Moreover, inactivation of the visual cortex with topical lignocaine did not alter the directional bias of SSC neurones. Likewise, the directional bias of SSC neurones was not reduced by iontophoretic ejection of AP5 in the SSC. These data imply that NMDA receptors have an important role in mediating the cortical input to the SSC. However, cortical input does not appear to be responsible for conferring directional bias upon SSC neurones' visual responsiveness.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

The functional influence of nicotinic cholinergic receptors on the visual responses of neurones in the superficial superior colliculus.

In the rat, the superficial gray layer (SGS) of the superior colliculus receives glutamatergic projections from the contralateral retina and from the visual cortex. A few fibers from the ipsilateral retina also directly innervate the SGS, but most of the ipsilateral visual input is provided by cholinergic afferents from the opposing parabigeminal nucleus (PBG). Thus, visual input carried by cholinergic afferents may have a functional influence on the responses of SGS neurones. When single neuronal extracellular recording and iontophoretic drug application were employed to examine this possibility, cholinergic agonists were found to depress responses to visual stimulation. Lobeline and 1-acetyl-4-methylpiperazine both depressed visually evoked activity and had a tendency to reduce the background firing rate of the neurones. Carbachol depressed the visual responses without any significant effect on the ongoing activity, while the muscarinic receptor selective agonist methacholine increased the background activity of the neurones and reduced their visual responses. Lobeline was chosen for further studies on the role of nicotinic receptors in SGS. Given that nicotinic receptors are associated with retinal terminals in SGS, and that the activation of presynaptic nicotinic receptors normally facilitates transmitter release (in this case glutamate release), the depressant effects of nicotinic agonists are intriguing. However, many retinal afferents contact inhibitory neurones in SGS; thus it is possible that the increase in glutamate release in turn facilitates the liberation of GABA which goes on to inhibit the visual responses. We therefore attempted to reverse the effects of lobeline with GABA receptor antagonists. The depressant effects of lobeline on the visual response could not be reversed by the GABA(A) antagonist bicuculline, but the GABA(B) antagonist CGP 35348 reduced the effects of lobeline. We hypothesize that cholinergic drive from the parabigeminal nucleus may activate presynaptic nicotinic receptors on retinal terminals, thereby facilitating the release of glutamate onto inhibitory neurones. Consequently GABA is released, activating GABA(B) receptors, and thus the ultimate effect of nicotinic receptor activation is to depress visual responses.

Animals↗