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ABSTRACT: A systematic study of crystal lattice reorientation in early stages of recrystallization has been carried out to correlate the orientations of recrystallization nuclei with the deformation microtexture and with slip systems. Microstructure and texture of Al-1 wt.% Mn single crystals of unstable initial orientations of {112}111, {100}001 and {001}110 have been examined by high-resolution field-emission gun scanning electron microscope local orientation measurements. All single crystals were channel-die deformed at room temperature and then annealed for a short time. It was shown that often observed presence of the 112 directions as rotation axes in the formation of new nuclei orientation directly suggested a close link with the deformation process.
Journal of Microscopy 03/2010; 237(3):221-6. · 1.63 Impact Factor
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ABSTRACT: The crystallography of recrystallization has been investigated in channel-die deformed pure aluminium bicrystals with {100}<011>/{110}<001> orientations. The microstructural and microtextural changes during the early stages of recrystallization were followed by systematic local orientation measurements using scanning and transmission electron microscopes. In particular, orientation mapping combined with in situ sample heating was used to investigate the formation and growth of new grains at very early stages of recrystallization. Grain boundary migration and 'consumption' of the as-deformed areas was always favoured along directions parallel to the traces of the {111} slip planes that had been most active during deformation.
Journal of Microscopy 09/2006; 223(Pt 3):264-7. · 1.63 Impact Factor
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ABSTRACT: The frontal cortex is innervated by serotonergic terminals from the raphe nuclei and it expresses diverse 5-HT receptor subtypes. We investigated the effects of 5-HT and different 5-HT receptor subtype-selective agonists on spontaneous discharges which had developed in rat cortical slices perfused with a Mg2+-free medium and the GABA(A) receptor antagonist picrotoxin. The frequency of synchronous discharges, recorded extracellularly in superficial layers (II/III) of the frontal cortex, was dose-dependently enhanced by 5-HT (2.5-40 microM). That excitatory effect was blocked by the 5-HT2 receptor selective antagonist ketanserin. The 5-HT2A/2C receptor-selective agonist DOI and the 5-HT4 receptor agonist zacopride also increased the frequency of spontaneous discharges. In the presence of ketanserin, 5-HT decreased the discharge rate; a similar effect was observed when the 5-HT1A receptor agonist 8-OH-DPAT or the 5-HT1B receptor agonist CGS-12066B was applied. The 5-HT3 receptor agonist m-CPBG was ineffective. In conclusion, 5-HT produces multiple effects on epileptiform activity in the frontal cortex via activation of various 5-HT receptor subtypes. The excitatory action of 5-HT, which predominates, is mediated mainly by 5-HT2 receptors. The inhibitory effects can be attributed to activation of 5-HT1A and 5-HT1B receptors.
Journal of physiology and pharmacology: an official journal of the Polish Physiological Society 07/2001; 52(2):265-74. · 2.27 Impact Factor
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ABSTRACT: Using extracellular and intracellular ex vivo recording techniques we studied changes in the reactivity of hippocampal pyramidal CA1 neurons to serotonin (5-HT) and to the 5-HT1A- and 5-HT4 receptor agonists (+/-)-2-dipropylamino-8-hydroxy- 1,2,3 ,4-tetrahydronaphthalene hydrobromide (8-OH-DPAT) and zacopride, respectively, evoked by repeated electroconvulsive shock (ECS), imipramine and corticosterone treatments. Rats were subjected to ECS for 1 or 10 days, treated with imipramine for 1, 7, 14 or 21 days (10 mg/kg p.o., twice daily) and with corticosterone for 7 days (10 mg/kg s.c., twice daily). Hippocampal slices were prepared 2 days after the last treatment. Activation of 5-HT1A receptors decreased the amplitude of population spikes evoked by stimulation of the Schaffer/collateral-commissural pathway and hyperpolarized CA1 cells. Activation of 5-HT4 receptors increased the population spike amplitude and decreased the amplitude of slow afterhyperpolarization. Both repeated ECS and imipramine enhanced the effects related to 5-HT1A receptor activation and attenuated the effects of 5-HT4 receptor activation. The action of imipramine was significant after a 7-day treatment and reached a maximum after 14 daily applications, remaining at the same level in a group of animals treated for 21 days. Repeated corticosterone attenuated the inhibitory effect of 5-HT and 8-OH-DPAT on the population spike amplitude and enhanced the increase in population spike amplitude induced by zacopride. These findings indicate that antidepressant treatments and repeated corticosterone have opposite effects on hippocampal responsiveness to 5-HT1A and 5-HT4 receptor activation. In consequence, antidepressants enhance, whereas corticosterone reduces the 5-HT-mediated inhibition of hippocampal CA1 cells, which may be relevant to the antidepressant and pro-depressant effects of either treatment, respectively.
Archiv für Experimentelle Pathologie und Pharmakologie 06/2001; 363(5):491-8. · 2.65 Impact Factor
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ABSTRACT: Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizures and epileptogenesis. In the present experiments, the selective, group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY354740, 0.1-1.0 microM) inhibited spontaneous epileptiform discharges which developed in rat cortical slices in Mg2+-free medium. LY354740 (4-16 mg/kg) administered prior to an injection of pentylenetetrazol (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions, but had no effect on N-methyl-D-aspartate (NMDA, 150 mg/kg)-induced convulsions. LY354740 (4-16 mg/kg) did not affect lethality induced in mice by pentylenetetrazol, picrotoxin or NMDA. LY354740 potentiated the anticonvulsant activity of the conventional antiepileptic drug diazepam, significantly decreasing the ED50 for that drug's effect on pentylenetetrazol-induced convulsions by 30%, but had no influence on anticonvulsant activity of ethosuximide and valproic acid. A pharmacokinetic interaction between LY354740 and diazepam, leading to the lowering of the plasma level of free diazepam, was also demonstrated. Our data suggest that the group II mGluR agonist LY354740 possesses anti-seizure activity and may modify the effects of some conventional antiepileptic drugs.
Archiv für Experimentelle Pathologie und Pharmakologie 04/2000; 361(3):283-8. · 2.65 Impact Factor
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ABSTRACT: Disturbances in the serotonin (5-HT) system and the limbic-hypothalamo-pituitary-adrenal axis (LHPA) have been implicated in the pathophysiology of depression. It is well established that hippocampus is a central component of limbic circuitry that participates in the modulation of cognition, mood and behavior, and is involved in the control of the LHPA axis. Therefore, the hippocampus provides a unique environment to study the interplay between serotonergic system, antidepressants and corticosteroids. Activity of hippocampal cells can be modulated by 5-HT via inhibitory 5-HT1A and excitatory 5-HT4 receptors. Repeated treatment with antidepressants increases the responsiveness of hippocampal pyramidal neurons to the 5-HT1A and attenuates the responsiveness to the 5-HT4 receptor agonists, with a time course which correlates with the delayed onset of the therapeutic effect of antidepressants in humans. Moreover, repeated corticosterone, which may constitute a model of a prolonged nonadaptable stress, has opposite effect on hippocampal responsiveness to the 5-HT1A and 5-HT4 receptor activation. Such an action results in an enhancement of the 5-HT-mediated inhibition by antidepressants and a reduction in the inhibitory effect of 5-HT by corticosterone which may be relevant to antidepressant/antiaxiety and proaxiety effects, respectively, of both treatments.
Postȩpy higieny i medycyny doświadczalnej 02/2000; 54(3):391-401.
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M Bijak
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ABSTRACT: Neuropeptide Y reduced spontaneous and stimulation-evoked epileptiform discharges in rat frontal cortex slices perfused with a magnesium-free solution and with the GABA(A) receptor antagonist picrotoxin. To investigate the mechanism of that action, effects of neuropeptide Y on intrinsic membrane properties and synaptic responses of layer II/III cortical neurons were studied using intracellular recording. Neuropeptide Y (1 microM) had no detectable effect on the membrane properties of neurons. The evoked synaptic potentials were attenuated by neuropeptide Y. Moreover, the pharmacologically isolated excitatory postsynaptic potentials, mediated by N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors, were reversibly depressed by neuropeptide Y. The most pronounced inhibitory effect of neuropeptide Y was observed on late polysynaptic excitatory postsynaptic potentials. To assess a putative postsynaptic action of neuropeptide Y, N-methyl-D-aspartate was locally applied in the presence of tetrodotoxin. The N-methyl-D-aspartate-evoked depolarizations were unaffected by neuropeptide Y, which suggests that the depression of excitatory postsynaptic potentials was due to an action at sites presynaptic to the recorded neurons. These data show that neuropeptide Y attenuates epileptiform discharges and the glutamate receptor-mediated synaptic transmission in the rat frontal cortex. The above results indicate that neuropeptide Y may regulate neuronal excitability within the cortex, and that neuropeptide Y receptors are potential targets for an anticonvulsant therapy.
Neuroscience 02/2000; 96(3):487-94. · 3.38 Impact Factor
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ABSTRACT: Evidence suggests that metabotropic glutamate receptors (mGluR) are involved in mediating seizures and epileptogenesis. In the present experiments, the selective, group II mGluR agonist (+)-2-aminobicyclo-[3.1.0]hexane-2,6-dicarboxylic acid (LY354740, 0.1-1.0 M) inhibited spontaneous epileptiform discharges which developed in rat cortical slices in Mg2+- free medium. LY354740 (4-16 mg/kg) administered prior to an injection of pentylenetetrazol (80 mg/kg) or picrotoxin (3.2 mg/kg) produced a dose-dependent decrease in the number of mice exhibiting clonic convulsions, but had no effect on N-methyl-d-aspartate (NMDA, 150 mg/kg)-induced convulsions. LY354740 (4-16 mg/kg) did not affect lethality induced in mice by pentylenetetrazol, picrotoxin or NMDA. LY354740 potentiated the anticonvulsant activity of the conventional antiepileptic drug diazepam, significantly decreasing the ED50 for that drug's effect on pentylenetetrazol-induced convulsions by 30%, but had no influence on anticonvulsant activity of ethosuximide and valproic acid. A pharmacokinetic interaction between LY354740 and diazepam, leading to the lowering of the plasma level of free diazepam, was also demonstrated. Our data suggest that the group II mGluR agonist LY354740 possesses anti-seizure activity and may modify the effects of some conventional antiepileptic drugs.
Archiv für Experimentelle Pathologie und Pharmakologie 01/2000; 361(3):283-288. · 2.65 Impact Factor
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ABSTRACT: Imipramine, a serotonin and noradrenaline uptake inhibitor, is the prototypical tricyclic antidepressant. The effects of imipramine on neuronal responsiveness to the group I glutamate metabotropic (mGlu) receptor agonist (RS)-3,5-dihydroxyphenylglycine (DHPG) were studied ex vivo, in the CA1 area of rat hippocampus, using extracellular and intracellular recording. DHPG increased the population spike amplitude, depolarized CA1 cells and decreased the slow afterhyperpolarization. Imipramine (20 microM) administered acutely in vitro did not change the effect of DHPG on population spikes. Repeated treatment with imipramine (10 mg/kg, twice daily, for 14 days) significantly attenuated the enhancing effect of DHPG (2.5 and 5 microM) on population spikes, as well as the DHPG-induced depolarization and the decrease in the slow afterhyperpolarization. Repeated treatment with imipramine had no effect on passive or active membrane properties of CA1 pyramidal cells. The results of the time-course experiment demonstrated that the imipramine-induced decrease in the responsiveness of CA1 cells to DHPG was apparent after a 7-day treatment; there was a further decrease after 14 days of treatment to a level which was not changed by longer (21-day) administration of imipramine. The attenuation of neuronal responsiveness to DHPG induced by a 14-day treatment was still detectable 7 days after imipramine withdrawal. It is concluded that repeated treatment with imipramine induces a decrease in the responsiveness of rat CA1 hippocampal neurons to group I mGlu receptor activation with a time course which correlates with the delayed onset of the therapeutic effect of antidepressants in humans. This suggests that alterations in mGlu receptors may contribute to antidepressant efficacy.
European Journal of Pharmacology 12/1999; 386(2-3):173-9. · 2.52 Impact Factor
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M Bijak
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ABSTRACT: Neuropeptide Y (NPY) and different NPY receptor (Y) subtype-selective agonists were tested for their effects on spontaneous epileptiform discharges which developed in rat cortical and hippocampal slices in Mg(2+)-free medium. Epileptiform activity, recorded extracellularly, was attenuated by NPY (0.5-1 microM) in both the frontal cortex and hippocampal CA3/CA1 pyramidal cell layers. In the cortex the Y1/5 selective agonist [Leu31 Pro34] NPY was more effective than the Y2 preferring agonist NPY13-36 and the Y2/5 preferring agonist NPY3-36. The suppression of epileptiform discharges induced by NPY in cortical slices was blocked by the selective Y1 receptor antagonist (R)-N2-(diphenylacetyl)-N-((4-hydroxyphenyl)methyl] argininamide (BIBP 3226). In the hippocampus, NPY13-36 and NPY3-36 were more effective than [Leu31 Pro34] NPY. In conclusion, the antiepileptic activity of NPY is mediated predominantly by the Y1 receptor subtype in the frontal cortex and by Y2 and probably Y5 receptors in the hippocampal CA3/CA1 areas.
Neuroscience Letters 07/1999; 268(3):115-8. · 2.11 Impact Factor
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ABSTRACT: We investigated the effects of repeated electroconvulsive shock or imipramine treatment on inositol phosphate accumulation and on the reactivity of neurons to metabotropic glutamate (mGlu) receptor agonists in rat hippocampal slices. (1S,3R)-1-carboxycyclopentane-3-acetic acid (1S,3R-ACPD), a nonselective mGlu receptor agonist, caused a concentration-dependent increase in inositol phosphate in slices from the CA1 region of the hippocampus, an effect that was not modified by imipramine or electroconvulsive shock treatment. 1S,3R-ACPD or the selective agonist of the I group of mGlu receptor, (R,S)-3,5-dihydroxyphenylglycine ((R,S)-3,5-DHPG), produced a concentration-dependent increase of the population spike recorded in the CA1 cell layer. This effect of 1S,3R-ACPD was markedly attenuated by both repeated imipramine and electroconvulsive shock treatment, and the action of (R,S)-3,5-DHPG was markedly attenuated by prolonged imipramine treatment (electroconvulsive shock was not tested). Our results indicate that antidepressant treatment may induce a subsensitivity of group I mGlu receptors when assessed by electrophysiological but not biochemical measures.
European Journal of Pharmacology 06/1998; 349(1):83-7. · 2.52 Impact Factor
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ABSTRACT: The role of serotonin1A and serotonin4 receptors in the modulation of synaptic inhibition in the dentate gyrus of guinea-pig hippocampal slices was studied. The effects of serotonin (5-hydroxytryptamine) on hilar neurons and on inhibitory postsynaptic potentials in granule cells were compared using intracellular recording in the presence of glutamatergic receptor antagonists. On the basis of electrophysiological properties hilar neurons were classified as type I neurons (presumably inhibitory) and type II neurons (presumably excitatory). Serotonin hyperpolarized a proportion of type I hilar neurons (60%) and decreased their input resistance through activation of a K+-conductance. This effect was mediated by serotonin1A receptors since it was mimicked by the selective serotonin1A receptor agonist (+/-)-8-hydroxy-dipropylaminotetralin hydrobromide and blocked by the selective serotonin1A receptor antagonist (+) WAY 100135. In some type I hilar neurons (40%) neither serotonin nor (+/-)-8-hydroxydipropylaminotetralin hydrobromide induced a membrane hyperpolarization. Instead, serotonin induced an excitatory response, depolarizing the cells and blocking the slow afterhyperpolarization. Similar effects were seen in all hilar neurons after blockade of serotonin1A receptors. They were mimicked by the serotonin4 receptor agonist zacopride. Serotonin induced either decreases or increases in the frequency of spontaneous GABA(A) receptor-mediated inhibitory postsynaptic potentials in granule cells via activation of serotonin1A and of serotonin4 receptors, respectively. 4-aminopyridine-evoked GABA(B) receptor-mediated inhibitory postsynaptic potentials were inhibited by serotonin via activation of serotonin1A receptors. However, after blockade of serotonin1A receptors, serotonin increased the frequency of GABA(B)-inhibitory postsynaptic potentials through the activation of serotonin4 receptors. We conclude that a proportion of inhibitory neurons in the dentate area does not express serotonin1A receptors and is excited by serotonin. Other inhibitory neurons express serotonin1A receptors and are inhibited by serotonin.
Neuroscience 07/1997; 78(4):1017-26. · 3.38 Impact Factor
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ABSTRACT: The effect of repeated treatment with various antidepressant drugs on the reactivity of CA1 neurons to the 5-HT4 receptor agonist zacopride was examined. Zacopride decreased the calcium-activated afterhyperpolarization and adaptation, it also elicited a slow membrane depolarization associated with an increase in input resistance. All those effects may have contributed to the zacopride-induced increase in the amplitude of population spikes, evoked in the CA1 cell layer by stimulation of the Schaffer collateral/commissural pathway. The later effect of zacopride was concentration-dependent and was antagonized by the 5-HT4 receptor antagonist DAU 62805. Repeated (14 days, twice daily), but not single, administration of the antidepressant drugs imipramine, citalopram, fluvoxamine and paroxetine (10 mg/kg) attenuated the effect of zacopride on population spikes. Because inhibitory 5-HT1A and excitatory 5-HT4 receptors are colocalized on pyramidal neurons, and our previous data demonstrated an increase in the 5-HT1A receptor-mediated inhibition after repeated treatment with antidepressants, we conclude that treatment with antidepressant drugs may enhance the inhibitory effect of 5-HT directly, by increasing the 5-HT1A receptor responsiveness, and indirectly, by inducing subsensitivity to the 5-HT4 receptor activation.
Archiv für Experimentelle Pathologie und Pharmakologie 02/1997; 355(1):14-9. · 2.65 Impact Factor
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ABSTRACT: Effects of paroxetine (10 mg/kg PO, twice daily, 14 days) on 5-HT receptor subpopulations in the brain were evaluated pharmacologically, electrophysiologically and biochemically in male Wistar rats. Imipramine was used for comparison. Repeated paroxetine antagonized the 8-OH-DPAT-induced behavioural syndrome (a 5-HT1A effect); imipramine showed similar, yet weaker, activity. The 5-HT-or 8-OH-DPAT-induced inhibition of population spikes in hippocampal slices was increased by both those repeated antidepressants. Repeated (or acute) paroxetine decreased the density of and increased the affinity for 5-HT1A receptors ([3H]-8-OH-DPAT used as ligand) in the hippocampus, while imipramine induced opposite effects. m-Chlorophenyl piperazine (m-CPP)-evoked exploratory hypoactivity, a 5-HT2C effect, was reduced by repeated paroxetine, but not by imipramine. Either of the antidepressants given repeatedly antagonized TFMPP-induced hyperthermia (another putative 5-HT2C effect). 5-HTP-induced head twitches (a 5-HT2A effect) were inhibited by repeated paroxetine or imipramine. Either antidepressant given repeatedly decreased the density of 5-HT2A receptors ([3H]-ketanserin as a ligand) in the brain cortex, but did not change their affinity. The present results indicate that paroxetine given repeatedly induces secondary changes in 5-HT2 receptors, which lead to reduction of the 5-HT2 neurotransmission (reduced responsiveness of 5-HT2 postsynaptic receptors). The consequences of the secondary changes in 5-HT1A receptors, found here still await clarification.
Psychopharmacology 10/1996; 127(1):73-82. · 4.08 Impact Factor
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ABSTRACT: The effect of repeated treatment with imipramine on the 5-HT1A receptor-mediated inhibition of a population spike was studied in the rat CA1 hippocampal region ex vivo. Serotonin (5-hydroxytryptamine, 5-HT) and the selective 5-HT1A receptor agonist 8-hydroxy-2-(dipropylamino)tetralin (8-OH-DPAT) decreased dose-dependently the amplitude of population spikes; this effect was blocked by the selective 5-HT1A receptor antagonist (S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazin-1-yl]-2-phenylpro panamide dihydrochloride [(S)-WAY 100135]. Repeated (14 days, twice daily), but not single, administration of imipramine (10 mg/kg) shifted the dose-response curves for serotonin and 8-OH-DPAT to the left. Repeated treatment with imipramine did not change the density of 5-HT1A receptors in the hippocampus as measured by autoradiography using [3H]8-OH-DPAT as a ligand. The latter findings indicate that the imipramine-induced increase in the responsiveness of hippocampal neurons to stimulation of 5-HT1A receptors may not involve an increase in the density of this receptor subtype. To find out whether the efficacy of the postreceptor transduction mechanism is changed by repeated treatment with imipramine, we examined the effect of baclofen. The baclofen-induced inhibition of the population spike was not changed by imipramine. Our results suggest that repeated treatment with imipramine induces sensitization to the inhibitory effects of 5-HT1A receptor agonists in the hippocampus.
European Journal of Pharmacology 07/1996; 305(1-3):79-85. · 2.52 Impact Factor
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ABSTRACT: The effect of neuropeptide Y (NPY) on the picrotoxin-induced activity was studied in rat brain hippocampal slices in vitro and after intrahippocampal injection in vivo. In the hippocampal slices, NPY (0.1-0.5 microM) inhibited the picrotoxin-induced epileptiform activity recorded extracellularly in CA1 and CA3 hippocampal pyramidal cells. Similar inhibition was induced by the Y2 receptor agonist NPY13-36, which indicates that the effect of NPY was due to activation of Y2 receptors. In behavioural studies, rats with chronically implanted cannulae were injected unilaterally into the CA1 hippocampal region with a 1 ml volume of the studied substances. Picrotoxin in a dose of 1 mg (1.6 nmol) induced behavioural excitation, shakes and weak signs of epileptic behaviour. NPY in a dose of 2 mg (470 pmol), but not 1 mg, inhibited some excitatory effects of picrotoxin, but did not change the epileptic symptoms. The obtained results suggest that NPY has an inhibitory action in the hippocampus, which can be observed in vitro and also in a behavioural study.
Neuropeptides 03/1996; 30(1):7-12. · 1.55 Impact Factor
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ABSTRACT: Double intracellular recording from granule cells and hilar neurons was performed in hippocampal slices to study the effect of gamma-aminobutyric acid (GABA) receptor antagonists on the activity induced by the convulsant 4-aminopyridine (4-AP) in the dentate gyrus. 4-AP evoked GABA-mediated responses in granule cells and burst discharges in hilar neurons. In the presence of GABAB but not GABAA receptor antagonists, 4-AP evoked discharge activity in dentate granule cells. When both GABAA and GABAB receptors were blocked 4-AP induced synchronous 'paroxysmal depolarizing shift'-like activity in granule cells and hilar neurons. Our data indicate that GABAB receptor-mediated mechanisms protect dentate cells against the convulsant effects of 4-AP.
Neuroscience Letters 03/1996; 205(1):49-52. · 2.11 Impact Factor
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ABSTRACT: The effect of repeated treatment with antidepressant drugs imipramine, (+)oxaprotiline and paroxetine on neuronal responsiveness to 5-HT and the 5-HT1A receptor agonist 8-OH-DPAT was examined in the hippocampal slice preparation from the rat. 5-HT and 8-OH-DPAT decreased the amplitude of population spikes evoked in the CA1 cell layer by electrical stimulation of the stratum radiatum. The antidepressant drugs, administered for 2 weeks, produced a significant increase in the inhibitory effect of 5-HT and 8-OH-DPAT. Repeated treatment with imipramine did not change the density of 5-HT1A receptors in the hippocampus suggesting that the increase in 5-HT1A responsivity may not involve an increase in the receptor density.
Acta Physiologica Hungarica 02/1996; 84(3):343-4. · 0.82 Impact Factor
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M Bijak
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ABSTRACT: Changes in the strength of synaptic inhibition have profound effects on the functions of cortical neurones. Accumulating evidence suggests that inhibitory synaptic transmission may be the target of actions of monoamines. In the hippocampal dentate gyrus, norepinephrine and serotonin (5-HT) have multiple direct and indirect actions on the presumed inhibitory hilar neurones. These effects are mediated through distinct mechanisms and signalled by different receptor subtypes. The predominant effects of norepinephrine are excitatory and are mediated by beta-adrenergic receptors. Accordingly, both the GABAA- and GABAB-receptor-mediated inhibition in granule cells is enhanced by activation of the beta-adrenergic receptor. 5-HT has more complex effects inhibiting a subpopulation of the hilar neurones and exciting other hilar cells. Study of the effects of 5-HT on inhibition in granule cells revealed that 5-HT enhanced Cl-IPSPs and blocked K-IPSPs. These results are in line with the suggestion that Cl- and K-IPSPs in granule cells are generated by two distinct populations of inhibitory neurones.
Acta neurobiologiae experimentalis 02/1996; 56(1):385-95. · 2.11 Impact Factor
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ABSTRACT: To study the effects of norepinephrine on synaptic inhibition in the dentate gyrus, intracellular recordings were made from hilar neurons in the guinea-pig hippocampal slice. The effects of norepinephrine on hilar neurons were compared with changes in the frequency of spontaneous inhibitory postsynaptic potentials recorded from granule cells. Hilar neurons comprised two electrophysiologically distinct groups: type I hilar neurons displayed a pronounced single spike afterhyperpolarization and little spike frequency accommodation, type II hilar neurons had small afterhyperpolarizations and pronounced spike frequency accommodation. The majority of recordings were from type I hilar neurons which are presumably inhibitory to granule cells. In most instances, effects of norepinephrine (2-10 microM) on hilar neurons could be mimicked by the beta-adrenergic agonist isoproterenol (0.1-1 microM). Isoproterenol induced a slight depolarization, blocked a slow afterhyperpolarization and, in type II neurons, reduced spike frequency accommodation. These effects were associated with an increase in the spontaneous discharge rate and an enhancement of spontaneous excitatory and inhibitory postsynaptic potentials. In accordance, isoproterenol and norepinephrine increased the frequency of inhibitory postsynaptic potentials in granule cells. In the presence of the non-N-methyl-D-aspartate receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione and the N-methyl-D-aspartate receptor antagonist CGP 37849, isoproterenol and norepinephrine also increased the frequency of Cl- -dependent inhibitory postsynaptic potentials in granule cells. Under this experimental condition, however, norepinephrine reduced the discharge rate of type I hilar neurons through an effect on alpha-receptors. In the presence of GABAA receptor blockers, norepinephrine increased the frequency of spontaneously occurring K(+)-dependent inhibitory postsynaptic potentials in granule cells. Accordingly, the frequency of burst discharges in type I hilar neurons was increased. We suggest that the discrepancy in the effect of norepinephrine on the discharge rate of presumed inhibitory hilar neurons and the frequency of Cl- -dependent inhibitory postsynaptic potentials in granule cells results from a direct effect of norepinephrine on GABAergic terminals because norepinephrine also enhanced the frequency of tetrodotoxin-resistant inhibitory postsynaptic potentials in granule cells. Thus, the net effect of synaptically released norepinephrine on synaptic inhibition in the dentate gyrus will be determined by opposing actions of alpha- versus beta-receptor stimulation at the synapse on hilar neurons.
Neuroscience 09/1995; 67(3):541-50. · 3.38 Impact Factor
