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R S Neuman

Publications and source records attributed to R S Neuman.

34 records · Page 2Linked to original sources
PubMed1988

Antagonism of spontaneous and evoked bursts by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the CA3 region of the in vitro hippocampus.

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) antagonized kainate-induced bursts and bursts of unknown origin in the CA3 region. CNQX also increased the latency of and eventually blocked evoked bursts which persist following kainate washout. In contrast, D-(-)-2-amino-7-phosphonoheptanoic acid did not alter burst latency or block bursts unless applied subsequent to CNQX. We conclude that the quisqualate type receptor has a prominent role in burst generation with a smaller contribution from N-methyl-D-aspartate receptors.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1988

Blockade of excitatory synaptic transmission by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in the hippocampus in vitro.

Superfusion of hippocampal slices with 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 2-5 microM) reversibly blocked the Schaffer collateral and mossy fibre excitatory postsynaptic potential (EPSP), while sparing the fast and slow gamma-aminobutyric acid (GABA)-mediated inhibition. Membrane potential, input resistance and spike accommodation were not altered. Inward currents induced by quisqualate were reduced to a greater extent by CNQX than those induced by kainate or N-methyl-D-aspartate. We suggest that CNQX may be a useful antagonist to study excitatory amino acid-mediated synaptic transmission.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1986

Suppression of penicillin-induced epileptiform activity by noxious stimulation: mediation by 5-hydroxytryptamine.

Noxious stimulation has a well known suppressant effect on epileptiform activity in both laboratory animals and man. To study this phenomenon in an animal model, focal epileptiform activity was induced in anaesthetized rats by applying penicillin from one barrel of a micropipette while recording intracortical electrical activity from another barrel. Penicillin produced either focal epileptiform activity or focal penicillin spikes, depending somewhat on the rate of penicillin release. Focal epileptiform activity was suppressed by noxious stimulation, both somatic and olfactory, whereas non-noxious stimulation was ineffective in this regard. Focal penicillin spikes were only rarely suppressed by noxious stimulation. Reserpine blocked the suppressant effect of noxious stimulation as did p-chlorophenylalanine, a more selective depletor of 5-hydroxytryptamine. L-5-Hydroxytryptophan, a 5-hydroxytryptamine precursor, restored the suppressant effect of noxious stimulation blocked by reserpine and p-chlorophenylalanine. These results suggest that the suppression of SW by noxious stimulation is mediated by 5-hydroxytryptamine. Data from experiments employing pharmacological antagonists suggest the suppression of spike and wave activity by noxious stimulation not to be mediated by activation of dopamine receptors, alpha 2 or beta adrenoceptors, or muscarinic cholinoceptors. Prazosin, a selective alpha 1 adrenoceptor antagonist, did block the suppressant effect of noxious stimulation but only at a very high dose (2.4 mumols/kg). This likely reflects a known analgesic action of prazosin or weak binding to the 5-HT receptor. Methysergide, a 5-hydroxytryptamine antagonist, failed to antagonize the suppressant effect of noxious stimulation, however, many inhibitory actions of 5-hydroxytryptamine are not blocked by methysergide. It is concluded that suppression of focal epileptiform activity by noxious stimulation is mediated, at least in part, by 5-hydroxytryptamine.

5-Hydroxytryptophan↗
PubMed1985

Action of serotonin and norepinephrine on spinal motoneurones following blockade of synaptic transmission.

The actions of serotonin and norepinephrine were investigated on spinal motoneurones in isolated, hemisected rat and frog spinal cords. Serotonin and norepinephrine induced slowly developing depolarizations of spinal motoneurones which were frequently preceded by brief, low amplitude hyperpolarizations. Neither the depolarizations nor the hyperpolarizations were attenuated by 20 mM Mg2+ or tetrodotoxin, although synaptic transmission was blocked in both cases. It thus appears unlikely that the action of serotonin and norepinephrine on spinal motoneurone polarization and results from an indirect action via interneurones.

Animals↗
PubMed1984

Selective accumulation of hydroxytryptamines by frog tectal neurones.

By means of histofluorescence microscopy, 5,7-dihydroxytryptamine was shown to be taken up by selective populations of brain neurones of the frog, Rana pipiens, following both intracranial administration and in vitro incubation with isolated brain preparations. Presumptive non-aminergic cell bodies of the superficial aspect of tectal lamina 6 exhibited more avid uptake than did putative serotonin perikarya of the raphe complex. Within the tectum, 5,7-dihydroxytryptamine uptake appeared to be restricted to large piriform neurons; in the torus semicircularis, it occurred in a morphologically dissimilar group of scattered cells. The same tectal cell system accumulated 5-hydroxytryptamine and 6-hydroxytryptamine, but not N-acetylserotonin, melatonin, or noradrenaline. 5,7-Dihydroxytryptamine uptake was insensitive to cold or imipramine; however, it was blocked by ouabain at high but not low temperature. At concentrations greater than or equal to 100 microM, 5,7-dihydroxytryptamine-induced fluorescence was sufficiently intense to permit tracing of intratectal dendrites and tectofugal axonal processes projecting to a lateral diencephalic neuropil and an ipsilateral isthmic neuropil. While previous monoamine histofluorescence and immunohistologic studies have not revealed serotonin-containing perikarya in the ranid tectum, our findings demonstrate that lamina 6 piriform projection neurones, presumably lacking indolamine-synthesizing enzymes, possess a striking capability for accumulating hydroxylated tryptamines.

5,7-Dihydroxytryptamine↗
PubMed1983

Long-lasting potentiation of the dentate gyrus population spike by norepinephrine.

The effects of iontophoretically applied norepinephrine (NE) on the dentate gyrus field potential evoked by perforant path stimulation were examined. NE potentiated the population spike by 20-400%, whereas the population EPSP was rarely increased. At 39% of the potentiated sites NE application resulted in long-lasting potentiation (LLP) suggesting a role for NE in long-term hippocampal plasticity.

Animals↗
PubMed1983

Pharmacological antagonism of facilitatory but not inhibitory effects of serotonin and norepinephrine on excitability of spinal motoneurons.

Serotonin (5HT) and norepinephrine (NE) produced long-lasting facilitation of glutamate-evoked activity of spinal motoneurons when applied iontophoretically with small ejection currents into the ventral horn. The facilitation was usually preceded by a brief period of inhibition at the onset of current application to the monoamine-containing barrels. This inhibition did not outlast the current application. Ejection of hydrogen ions produced only inhibition of glutamate-evoked activity with no subsequent facilitation at current offset. The 5HT antagonists, methysergide and metergoline, blocked the facilitation, but not the inhibition of motoneuron excitability caused by 5HT. Similarly, the alpha-adrenergic antagonists, piperoxane and phentolamine, blocked the facilitatory, but not the inhibitory, effects of NE on excitability of motoneurons. Since the inhibitory effects of 5HT and NE could not be blocked with the antagonists used, and since ejection of hydrogen ions also produced inhibition, non-specific causes for the inhibitory effects of 5HT and NE could not be rejected. However, the facilitatory effects of 5HT and NE on excitability of motoneurons were readily blocked by antagonists and were, therefore, attributed to actions on separate 5HT and NE receptors in the ventral horn.

Animals↗
PubMed1982

Serotonin-like actions of quipazine and CPP on spinal motoneurones.

The actions of iontophoretically applied quipazine (QPZ) and 6-chloro-2-[1-piperazinyl]-pyrazine (CPP) were compared with those of serotonin (5-HT) on rat spinal motoneurones. QPZ and CPP qualitatively resembled 5-HT in that both facilitated single unit activity evoked by glutamate. Like 5-HT, the facilitation they produced could be antagonized by metergoline or methysergide. These observations are compatible with the suggestion that the actions of QPZ and CPP are mediated by 5-HT receptors. In rats pretreated with the neurotoxin 5,7-dihydroxytryptamine (5,7-DHT), QPZ and CPP remained effective in facilitating the glutamate evoked activity, whereas p-chloroamphetamine (PCA), a known releaser of 5-HT, was without effect. In contrast, PCA produced a long lasting facilitation in untreated rats. These data, taken together, suggest that QPZ and CPP are direct agonists at 5-HT receptors, but do not preclude the possibility that they might also act indirectly.

5,7-Dihydroxytryptamine↗
PubMed1980

Facilitation of spinal motoneurone excitability by 5-hydroxytryptamine and noradrenaline.

The effects of iontophoretic application of 5-hydroxytryptamine (5-HT) and noradrenaline (NA) on lumbar motoneurone excitability were examined. 5-HT and NA produced long-lasting changes in motoneurone excitability as revealed by decreased threshold for glutamate-evoked motoneurone action potentials, increased rate of motoneurone firing evoked by suprathreshold amounts of glutamate and increased amplitude of ventral root and dorsal root evoked motoneurone field potentials. Neither 5-HT nor NA directly evoked motoneurone action potentials in the absence of other excitatory input. The 5-HT antagonist, methergoline, reduced glutamate-evoked motoneurone activity and prevented 5-HT, but not NA, facilitation of glutamate-evoked activity. These results suggest that 5-HT and NA enhance the effects of excitatory inputs to spinal motoneurones by actions on separate receptors.

Action Potentials↗
PubMed1979

Action of narcotic analgesics and antagonists on spinal units responding to natural stimulation in the cat.

Morphine and morphine-related agents were applied by microiontophoresis in the lumbar spinal cord of spinal cats to single units classified on the basis of their responses to natural cutaneous or proprioceptive stimulation. Opiate application had a current-dependent depressant effect on the ongoing activities of about one-third of the units tested. This effect was observed in laminae I and IV--VI, but only with units responding to noxious cutaneous stimuli: the nociceptive responses were themselves depressed. Excitatory and inhibitory responses to glutamate and gamma-aminobutyric acid, respectively, were also depressed. Intravenous administration of the opiates at doses reported to produce analgesia in the cat also depressed only units responding to noxious cutaneous stimuli, including their nociceptive responses. This depression could be reversed by either the iontophoretic application (100 nA) or the intravenous administration (0.1--0.8 mg/kg) of naloxone. These results are interpreted as further evidence that the analgesic effects of opiates are at least partly due to an action at the spinal level.

Action Potentials↗
PubMed1977

Effects of diphenylhydantoin and phenobarbital on voltage-clamped myelinated nerve.

Diphenylhydantoin (DPH) and phenobarbital (PB) have a selective action in blocking spontaneous activity in nerves made hyperexcitable by lowering the calcium concentration of the bathing medium (Rosenberg, P. and Bartels, E. 1967 J. Pharmacol. Exp. Ther. 155, 532-544.). To investigate this further, we examined the action of DPH and PB on voltage-clamped single myelinated nerves at two different calcium concentrations. In 1.8 mM calcium Ringer, DPH reduced the sodium permeability (PNa) without affecting the potassium conductance (GK) or the voltage-dependent time constants of sodium activation (taum) and inactivation (tauh), and potassium activation (taun). PB was similar to DPH except that in addition to reducing PNa, it shifted taum in the direction of depolarization. When the calcium concentration was lowered to 0.36 mM, the curves relating taum and taun to membrane potential were shifted in the direction of hyperpolarization, as expected. However, the addition of DPH or PB reduced or abolished these shifts. It is suggested that both DPH and PB stabilize hyperexcitable membranes by an action on the parameter m, and that this may contribute to their antiepileptic action.

Action Potentials↗
PubMedDate not supplied

Suppression of penicillin-induced focal epileptiform activity by locus ceruleus stimulation: mediation by an alpha 1-adrenoceptor.

Application of penicillin to the cerebral cortex of anesthetized rats by pressure ejection from a micropipette resulted in the appearance of focal epileptiform activity with low rates of penicillin release and focal penicillin spikes with higher rates. Electrical stimulation of the locus ceruleus (LC), a major norepinephrine-containing nucleus in the brainstem, or of its axons projecting to the forebrain, the dorsal noradrenergic bundle, suppressed penicillin-induced focal epileptiform activity but was less effective in suppressing focal penicillin spikes. Depletion of monoamines with reserpine blocked the suppressant effect of LC stimulation. Neither the selective depletion of 5-hydroxytryptamine with p-chlorophenylalanine nor administration of methysergide reduced the effectiveness of LC stimulation, suggesting that 5-hydroxytryptamine probably does not mediate the suppression. Pimozide partially antagonized the suppression of focal epileptiform activity induced by LC stimulation, which is consistent with antagonism of alpha-adrenoceptors but not dopamine receptors. beta-Receptor antagonists did not block the suppression of focal epileptiform activity by LC stimulation, suggesting that beta-receptors are not important in the observed suppression. Prazosin, a selective alpha 1-antagonist, at low doses blocked the suppression of focal epileptiform activity by LC stimulation whereas yohimbine, an alpha 2-antagonist enhanced the stimulation-induced suppression. Taken together, the data are consistent with LC and dorsal bundle stimulation releasing norepinephrine, which in turn suppresses focal epileptiform activity by an action mediated by an alpha 1-adrenoceptor.

Animals↗
PubMedDate not supplied

Serotonin mediates suppression of focal epileptiform activity induced by noxious stimulation.

Noxious stimulation can suppress epileptic seizures in humans and epileptiform activity in laboratory animals. Using as a model system the focal epileptiform activity (FEA) induced by the pneumophoresis of penicillin, the role of 5-hydroxytryptamine (5HT) in suppression of this activity by noxious stimulation was investigated. Drugs known to depress dorsal raphe unit activity, (+/-)-8-hydroxydipropylaminotetralin (DPAT), imipramine, and fluoxetine prevented suppression of FEA induced by noxious stimulation. Desimipramine, which depresses locus ceruleus but not dorsal raphe unit activity, was ineffective in blocking the suppression. Quipazine, an agonist at 5-HT receptors, in part restored the suppression that had been blocked by DPAT or imipramine. Several serotonin antagonists effective at 5-HT1 and 5-HT2 receptors blocked suppression, but an unequivocal determination of the serotonin receptor subtype mediating suppression could not be made. We conclude that 5-HT mediates suppression of FEA induced by noxious stimulation.

Animals↗