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H Matthies

Publications and source records attributed to H Matthies.

At least 19 recordsLinked to original sources
PubMed1992

Kindling and its consequences on learning in rats.

To study the learning performance of pentylenetetrazol- and amygdala-kindled Wistar rats we used the following learning tests: short-term memory was tested in the response-to-change model, brightness discrimination was tested in a Y-chamber, and two-way active avoidance learning was tested in a shuttle-box. Short-term memory was not impaired by both kindling procedures. Considering two-way active avoidance learning the performance of pentylenetetrazol (PTZ)-kindled rats was significantly diminished. This effect persists over a period of 4 weeks. However, amygdala (AMY)-kindled rats acquired this task like the controls. In brightness discrimination reaction (BDR) the learning performance of PTZ-kindled animals was not influenced. Although the acquisition of BDR was nearly identical, the 24-h retention was remarkably diminished in AMY-kindled rats. It was hypothesized that the different kindling procedures interfere in different ways and extent with neuronal circuits resulting in different functional impairments.

Amygdala↗
PubMed1992

The maintenance of hippocampal long-term potentiation is paralleled by a dopamine-dependent increase in glycoprotein fucosylation.

Induction of long-term potentiation (LTP) in hippocampal slices of rats caused an increase in both protein synthesis and glycoprotein fucosylation by 38 and 34%, respectively. The enhanced incorporation of [3H]fucose into glycoproteins observed 1 h after tetanization was abolished in the presence of the dopamine D1 receptor antagonist SCH23390 during stimulation whereas the LTP-induced increase of protein synthesis was not influenced by this drug. The enhanced insertion of [3H]fucose into hippocampal glycoproteins 1 h after tetanization was paralleled by an increase in the activity of the fucose metabolizing enzyme, fucokinase. In contrast no changes in protein and glycoprotein synthesis were detectable 5 h after tetanization of the slices. The results provide evidence that in addition to an enhanced protein synthesis a dopamine (D1) mediated increase in glycoprotein fucosylation is necessary for the maintenance of the late stage of LTP.

Animals↗
PubMed1992

Induction of expression of genes encoding transcription factors in the rat brain elicited by behavioral training.

c-fos and zif/268 are regulatory genes encoding transcription factors able to influence gene expression directly. It has been shown repeatedly that expression of transcription factors correlates with different forms of cell activation, probably being functionally involved in the coupling of extracellular signals with long-term cellular responses. This study describes that c-fos and zif/268 mRNA accumulation, as measured by northern blot analysis, occurs in the rat hippocampus as well as the visual cortex following behavioral training of two-way active avoidance response.

Animals↗
PubMed1992

Philanthotoxin-343 blocks long-term potentiation in rat hippocampus.

The effects of extracellularly-applied synthetic philanthotoxin-343 (PhTX-343) on transmission and long-term potentiation (LTP) at Schaffer-collateral/commissural-CA1 synapses were investigated. PhTX-343 was ineffective in antagonizing CA1 field-EPSPs mediated by AMPA/kainate receptors. However, when a micromolar concentration of the toxin was present during tetanization, the induction of LTP was suppressed. In contrast, when PhTX-343 was applied either immediately after or long after tetanization no effect on LTP could be found. It appears that the synaptic, non-NMDA receptors of the CA1-region are insensitive to PhTX-343. Suppression of LTP induction could result from antagonism of postsynaptic NMDA receptors, but the results do not rule out other possibilities such as presynaptic block.

Animals↗
PubMed1991

c-fos protooncogene expression in rat hippocampus and entorhinal cortex following tetanic stimulation of the perforant path.

The elevated expression of the c-fos protooncogene has been proposed to be a marker of cell activation leading to a long term cellular response. In this communication we compared the c-fos mRNA accumulation in the hippocampus (i.e. postsynaptic cells) and entorhinal cortex (i.e. presynaptic cells) following high (tetanic) and low frequency electrical stimulation of the perforant path. Using Northern blot analysis we have found that high frequency stimulation elevates c-fos expression in both hippocampus and entorhinal cortex, and the increase of c-fos mRNA levels in the entorhinal cortex is less pronounced, but longer lasting, than in the hippocampus. Slight increase of c-fos mRNA levels has been also observed in low frequency treated animals in the entorhinal cortex, but not in the hippocampus. These findings raise the question about differences in mechanisms involved in c-fos activation in both parts of the brain after stimulation which evokes long term potentiation (LTP) of synaptic efficacy.

Animals↗
PubMed1991

The effect of dopaminergic D1 receptor blockade during tetanization on the expression of long-term potentiation in the rat CA1 region in vitro.

The effect of dopaminergic D1 receptor blockade on the expression of long-term potentiation (LTP) was investigated in the rat hippocampal CA1 region in vitro by extracellular recordings (by measuring the population spike amplitude and the field EPSP). The presence of the very selective D1 receptor blocker SCH 23390 at a concentration of 0.1 microM during tetanization with 3 trains of 100 impulses (100 Hz) resulted in a prevention of late LTP stages (greater than 1-2 h). When SCH 23390 was added to the bath medium immediately after tetanization, an influence on established LTP could not be observed during the first 3 h investigated.

Animals↗
PubMed1991

The amnesic substance 2-deoxy-D-galactose suppresses the maintenance of hippocampal LTP.

Male Wistar rats were intraventricularly injected with 2-deoxy-D-galactose (do-gal), a substance interfering with the fucosylation of glycomacromolecules and impairing memory consolidation in various learning tasks. Do-gal was found to have no influence on the monosynaptically evoked field potential (MEFP) recorded in the dentate gyrus upon stimulation of the perforant pathway. However, hippocampal long-term potentiation (LTP) induced in do-gal-pretreated animals by fractionated tetanization of the perforant pathway declined to control levels 2 h after tetanization, whereas it remained constant for 24 h in saline-treated rats. Similar effects were observed in the CA1 region of hippocampal slices. The results indicate a participation of fucosylated macromolecules in the maintenance of LTP. The possible significance of processes involved in LTP for memory formation is discussed.

Amnesia↗
PubMed1991

Differential effects of protein kinase inhibitors on pre-established long-term potentiation in rat hippocampal neurons in vitro.

The possibility that a permanent protein kinase C (PKC) activity is necessary for the maintenance of long-term potentiation (LTP) was investigated in rat hippocampal slices. The action of the potent kinase inhibitors K-252a, K-252b and staurosporine on LTP of orthodromic population excitatory postsynaptic potentials (EPSPs) recorded from CA1 pyramidal cells was tested both during tetanization and after establishment of LTP. Confirming earlier studies, all inhibitors applied during tetanization at a concentration of 50 nM eliminate late LTP. Only staurosporine, but not K-252a or K-252b, blocked already established late LTP (i.e. late application). Normal synaptic transmission was influenced only weakly by staurosporine. Considering that all inhibitors have similar potencies against PKC and were all effective if applied during tetanization these data suggest that the late maintenance of LTP depends on a staurosporine/H7-sensitive process (or kinase) rather than permanent activation of PKC.

Alkaloids↗
PubMed1991

Enhanced development of morphine tolerance in rats treated with 2-deoxy-D-galactose.

Rats treated subcutaneously for 6 days with morphine developed a weak tolerance which was characterized by a decrease in the analgesic action of the opioid. Under those experimental conditions a simultaneous intracerebroventricular application of 2-deoxy-D-galactose enhanced development of morphine tolerance, while other deoxy-sugars like 2-deoxy-D-glucose and 6-deoxy-D-galactose were ineffective. In contrast, no influence of 2-deoxy-D-galactose on a more enhanced morphine tolerance after a 11-day pretreatment with morphine was found. The results are discussed in the light of a rather specific interference of 2-deoxy-D-galactose with neuronal glycoprotein processing and related cellular mechanism underlying adaptive processes involved in the development of morphine tolerance.

Analgesia↗
PubMed1991

Gangliosides improve a memory deficit in pentylenetetrazol-kindled rats.

Epileptic patients often show impairments in a number of cognitive functions. Kindling is considered to be a useful experimental model for human epilepsy. Recently we have demonstrated a learning impairment in a shuttle box experiment in pentylenetetrazol (PTZ)-kindled rats. This model offers the possibility to investigate the relation between repeated convulsions and their consequences on learning and on the other side to test the effectiveness of substances on both processes. Although systemic application of gangliosides has neither an effect on the development of seizures induced by repeated injections of PTZ, nor on seizures induced by PTZ in kindled animals, the treatment protects against the memory-impairing effect of convulsions. These findings suggest a new useful strategy in the therapy of epileptic patients with the aim of diminishing the psychosocial problems in persons with seizure disorders: a combination of the anticonvulsive basic therapy and gangliosides.

Animals↗
PubMed1991

Pharmacological effects on two inbred substrains of AB mice.

Mice of the two substrains AB/Gat and AB/Hal from the Jena AB inbred strain differ in behavior from each other by their aggressiveness occurring especially in the latter group after maturity. In order to ascertain the neurobiological background of aggressiveness, we injected mice of both substrains with either haloperidol, diazepam, or hexobarbital and measured their response on motor activity. In a second experiment, the reaction to a seizure evoking agent (pentylenetetrazol) was determined. Mice of both substrains were found to differ significantly in their reaction to haloperidol or diazepam injection. In contrast to that no changes in motor activity could be detected following hexobarbital administration. Animals of the aggressive AB/Hal substrain reacted more pronounced to pentylenetetrazol than those of the AB/Gat group. In conclusion, the varying aggressiveness of both AB mice substrains may be due to differences in dopaminergic and GABAergic neurotransmission.

Aggression↗
PubMed1991

Modulation of the antinociceptive effect of morphine by casomorphin derivatives.

Some D-amino acid-substituted derivatives of bovine beta-casomorphin1-5 (CM) were found to share a particular affinity to central opioid receptors. As far as the antinociceptive potency of CM derivatives and their ability to produce tolerance is concerned, possible interactions of two selected CMs (Tyr-Pro-Phe-D-Pro-Gly, D-Pro4 and Tyr-Pro-D-Phe-Pro-Gly, D-Phe3) with morphine and, moreover, the doses necessary to induce tolerance were studied. Antinociception was tested by using the hot-plate test in experiments with mice. It was found that both CMs injected in doses up to 1 mumol/kg were not able to produce any sign of antinociception. It is all the more so interesting since such non-antinociceptive doses of D-Phe3 decreased analgesia induced by 15 mumol/kg morphine significantly. This could be regarded as a consequence of delta-receptor occupation by D-Phe3 and a resulting shift in the mu-receptor-mediated signal transduction. Finally, we found that repeated applications (once daily over a period of 20 days) induced a detectable tolerance to morphine. This suggests that opioid analgesia and tolerance must not be mediated by the same mechanisms and, moreover, that the mechanisms responsible for the development of tolerance are able to react more sensitive to an opioid.

Amino Acid Sequence↗
PubMed1990

Proteolytic enzymes do not destroy the N-methyl-D-aspartate (NMDA) sensitivity of acutely isolated hippocampal CA1 and CA3 neurons from postnatal rats.

Using whole cell recordings in combination with the concentration clamp technique it was shown that even enzymatically isolated hippocampal CA1 and CA3 neurons exhibit N-methyl-D-aspartate (NMDA) and L-aspartate currents. These currents were completely blocked by 0.5 mM Mg2+ or partially blocked (72.7 +/- 2.4%) by DL-2-amino-5-phosphonovalerate (50 microM) whereas 10 microM glycine (Gly) potentiated the NMDA responses (3.1 +/- 1.6-fold). A half-maximum dose of 55 microM was calculated from the sigmoid NMDA dose-response curve in the presence of 10 microM Gly. The amplitudes of these currents did not depend on the type of the proteolytic enzyme used for cell isolation.

2-Amino-5-phosphonovalerate↗
PubMed1990

Transient increase of raf protein kinase-like immunoreactivity in the rat dentate gyrus during long-term potentiation.

Altered levels of cellular raf proteins (products of the raf protooncogenes) have been shown in the neurons of the dentate fascia of rats in response to high-frequency stimulation, with light microscopic immunohistochemistry by using polyclonal antibodies. No raf-1-like staining was seen in unstimulated tissue, while the pan-raf antibodies revealed immunoreactivity in the cytoplasm of neurons in the Ammon's horn and dentate fascia of rats and guinea pigs. The induction of long-term potentiation in the dentate fascia of freely-moving rats triggered the appearance of raf-1-like staining and increased the number of granule cells with pan-raf-like immunoreactivity. Since these proteins are serine/threonine-specific protein kinases, their appearance in long-term potentiation may indicate the activation of important cell membrane - nucleus transduction pathways.

Animals↗
PubMed1990

Dopaminergic antagonists prevent long-term maintenance of posttetanic LTP in the CA1 region of rat hippocampal slices.

The involvement of dopaminergic mechanisms in the induction and maintenance of posttetanic long-term potentiation (LTP) was investigated on CA1 cells of rat hippocampal slices. The presence of the dopamine receptor blocker domperidone in a concentration of 1 microM during tetanization with 3 trains of 100 impulses (100 Hz) and a train interval of 10 min influences neither the synaptic transmission nor the induction of LTP. However, the potentiation of both the population spike and the population EPSP gradually decreases, thus significantly differing from control LTP about 4 h after initiation and reaching the level of non-tetanized controls about 7-8 h after tetanization. The simultaneous presence of 1 microM apomorphine during tetanization abolishes this effect of domperidone indicating the specific dopaminolytic nature of its action. Also the presence of the dopamine antagonists sulpiride and flupenthixol, respectively, in a concentration of 1 microM during tetanization likewise prevents the occurrence of the late LTP maintenance. The determination of [14C]dopamine in 2 min fractions from the superfused slices after preloading during a preincubation period revealed that a low frequency stimulation of the Schaffer collaterals with 0.33 Hz does not influence the spontaneous efflux of dopamine, whereas the tetanization with an impulse train of 100 Hz produces a significantly enhanced release. The observations suggest that dopaminergic influences during and immediately after tetanization at least additionally contribute to the induction of postsynaptic mechanisms subserving a late, long-lasting maintenance of potentiation. The results also support the assumed existence of different subsequent stages of LTP.

Animals↗
PubMed1990

Properties of the fast sodium channels in pyramidal neurones isolated from the CA1 and CA3 areas of the hippocampus of postnatal rats.

The fast sodium (Na)current of hippocampal neurones was recorded using the intracellular perfusion method. Neurones were isolated from the CA1 and CA3 hippocampal subregions separately, after treatment of the tissue with trypsin. There were no differences between the current-voltage (I-V) characteristics of CA1 and CA3 neurones. In contrast to this, the steady-state inactivation (h infinity) of both types of neurones was significantly different. Additionally, there were two subpopulations of CA1 neurones, which showed different courses of h infinity. Compared with CA1 neurones, the steady-state activation and inactivation curves of CA3 neurones overlapped much more in the potential range -80 mV to -50 mV. These results are consistent with the well-known fact that CA3 neurones show spontaneous burst activity, while CA1 cells do not. The time constant of activation (tau m) depended upon the membrane potential in the same way for all CA3 neurones investigated. However, there were two different subpopulations of CA3 cells, showing different voltage dependence of the time constant of inactivation. We conclude that these differences reflect two types of pyramidal cells within the same subregion.

Animals↗