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Biomedical subjects

M Bijak

Publications and source records attributed to M Bijak.

71 records · Page 4Linked to original sources
PubMed1987

Excitatory and inhibitory action of dopamine on hippocampal neurons in vitro. Involvement of D2 and D1 receptors.

The study examined the effects of dopaminergic agonists on the extracellularly recorded spontaneous activity of CA1 neurons in hippocampal slices of the rat. Dopamine evoked excitation or inhibition of the neuronal firing rate, the first reaction being more sensitive to the substance. Having used selective dopaminergic agonists (pergolide and 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepines) and selective antagonists (haloperidol, spiperone, sulpiride and (R)-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3- benzazepine-7-ol), it was concluded that the excitation evoked by dopamine was due to activation of D2 dopamine receptors, while the inhibition was the result of D1 receptor activation. The effects of the dopamine agonists on the firing of CA1 neurons were long-lasting, which suggests a modulating role of dopamine in the hippocampus.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMed1986

Repeated imipramine treatment increases the responsivity of the rat hippocampus to dopamine. An in vitro study.

The sensitivity of hippocampal neurons to dopamine was studied in hippocampal slices obtained from rats treated acutely (10 mg/kg) or repeatedly (10 mg/kg, 14 days, twice a day) with imipramine. In non-treated rats dopamine induced a slight excitation or depression of the firing rate of CA 1 pyramidal neurons in slice preparations. Hippocampal slices prepared from the imipramine-treated rats displayed greater changes in the firing rate after dopamine application. Repeated imipramine administration also increased the number of slices sensitive to dopamine. it is concluded that repeated imipramine administration induces supersensitivity of hippocampal dopamine receptors.

Action Potentials↗
PubMedDate not supplied

Comparison of the effects of low and high concentrations of group I metabotropic receptor agonists on field potentials in the hippocampal CA1 region in vitro.

We compared the effects of low and high concentrations of the selective group I metabotropic glutamate receptor (mGluR) agonist (R,S)-3,5-dihydroxyphenylglycine (DHPG) and the nonselective mGluR agonist (1S,3R)-1-aminocyclopentane-1,3-dicarboxylic acid ((1S,3R)-ACPD) on extracellularly recorded potentials which were evoked in the rat hippocampal CA1 region by stimulation of the Schaffer collateral/commissural pathway and on intracellularly recorded electrophysiological properties of CA1 neurons, in vitro. At low concentrations (2.5 and 5 microM) DHPG and (1S,3R)-ACPD increased while at high concentrations (20 and 50 microM) they decreased population spike amplitudes. Simultaneous recordings of population spikes in the CA1 cell layer and field excitatory postsynaptic potentials (fEPSPs) in stratum radiatum of the CA1 area revealed that the enhancement of the population spike amplitude is not associated with any change in the fEPSP slope, but the decrease in population spikes is accompanied with a decrease in the fEPSP slope, suggesting that at high concentrations both agents may attenuate excitatory synaptic transmission in CA1 cells. DHPG and (1S,3R)-ACPD had a number of direct excitatory effects on CA1 pyramidal cells like a concentration-dependent depolarization and an inhibition of the slow afterhyperpolarization, which in all probability underlay the increase in the amplitude of population spikes. At high concentrations, both mGluR agonists strongly depolarized CA1 cells indicating that depolarization block of cell discharges may underlay the reduction in the population spike amplitude. Furthermore, robust cell discharges induced by the strong depolarizations, activate several secondary processes which may significantly contribute to the action of high concentrations of DHPG and (1S,3R)-ACPD. Therefore, the effects of low and high concentrations of the studied mGluR agonists may involve different mechanisms, at low concentrations the effects can be directly related to the activation of postsynaptically localized group I mGluRs while at higher concentrations the contribution of indirect effects may predominate.

Animals↗
PubMedDate not supplied

Imipramine-induced increase in the inhibitory effect of adenosine receptor activation in the hippocampus.

Imipramine, a tricyclic antidepressant, is one of the main drugs used for the treatment of depression. We investigated the effects of the repeated administration of imipramine (10 mg/kg po for 14 days, twice daily) on adenosine receptor-mediated actions using extracellular and intracellular recording techniques in the rat hippocampal slices. Adenosine and 2-chloroadenosine dose-dependently decreased the amplitude of population spikes and the slope of the field excitatory postsynaptic potentials (fEPSPs) evoked in the CA1 cell layer and apical dendrites of the CA1 cells, respectively, by stimulation of the Schaffer collateral/commissural pathway. As revealed by intracellular recording, a membrane hyperpolarization and a strong attenuation of excitatory synaptic transmission contribute to the decrease in the population spikes and fEPSPs induced by adenosine and 2-chloroadenosine. The repeated administration of imipramine enhanced the effect of adenosine (3 microM) and 2-chloroadenosine (0.15 microM) on fEPSPs while the inhibition of population spikes was not changed. When higher concentration of 2-chloroadenosine (0.25 microM) was tested, repeated imipramine administration enhanced its inhibitory effect on population spikes but not on fEPSPs. The present report provides evidence that the inhibitory effect of adenosine receptor activation in the hippocampus is enhanced by repeated treatment with imipramine.

2-Chloroadenosine↗
PubMedDate not supplied

Repeated corticosterone administration increases excitatory effect of 5-HT4 receptor agonist in the rat hippocampus.

The objective of the present study was to investigate whether repeated exposure of rats to high level of corticosterone affects responses of CA1 hippocampal cells to the 5-HT4 receptor agonist zacopride. To assess responsiveness of CA1 neurons to zacopride we used extracellular recording of population spikes evoked in CA1 cells by the stimulation of the Schaffer/collateral-commissural pathway in hippocampal slices. Rats were treated with corticosterone for 7 days (10 mg/kg sc, twice daily), slices were prepared two days after the last treatment. Zacopride induced an increase in the amplitude of population spike and repeated corticosterone treatment enhanced this excitatory effect. It is concluded that repeated treatment with corticosterone increases the responsiveness of hippocampal CA1 neurons to the 5-HT4 receptor activation.

Animals↗
PubMedDate not supplied

Electrophysiological effects of dopamine receptor stimulation in the hippocampus of Acomys cahirinus.

The effect of dopamine receptor agonists on the spontaneous bioelectrical activity of CA1 layer neurons in the hippocampal slice preparation from the Acomys and rat has been studied. The selective D1 receptor agonist SKF 38393 diminished the neuronal firing rate while the selective D2 receptor agonist LY 171555 (quinpirole) evoked an excitatory reaction, however, a great proportion of hippocampal neurons remained unresponsive to SKF 38393 and LY 171555. Both dopamine and apomorphine elicited mainly an increase in the neuronal discharge rate, the effect of the former having been antagonized by sulpiride. The present data reveal that the action of dopamine agonists on the hippocampal neurons of the Acomys generally resembles their activity on the rat hippocampal cells, however, the potency of dopamine and apomorphine in evoking the excitatory reaction is higher in the Acomys.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗
PubMedDate not supplied

Prolonged treatment with antidepressant drugs increases the excitatory effect of quinpirole in hippocampal slices.

The effects of single and repeated treatment with different antidepressant drugs, such as imipramine, mianserin and citalopram, on the responsiveness of the rat hippocampal neurons to the selective dopamine D-2 receptor agonist quinpirole were examined. The bath-applied quinpirole increased the firing rate of most of the studied CA1 layer neurons in a slice preparation. That excitatory response was attenuated by the selective D-2 receptor antagonist sulpiride. In hippocampal slices prepared from rats treated repeatedly with antidepressant drugs, the quinpirole-induced increase in the neuronal firing rate was significantly potentiated, compared to the quinpirole-induced effect in slices prepared from untreated animals. No change was observed in the reaction to quinpirole after a single dose of the antidepressant drugs used in the study. To determine whether the increase in the excitatory effect of quinpirole evoked by prolonged treatment with antidepressants is receptor-specific, or whether it reflects an unspecific increase in the neuronal responsiveness to excitatory agents, the effect of imipramine on the noradrenaline-induced excitation of CA1 neurons was studied. Prolonged, but not acute, treatment with imipramine decreased the beta-adrenergic receptor-mediated excitation evoked by noradrenaline. It is concluded that prolonged treatment with imipramine, mianserin and citalopram produces an increase in the responsiveness of hippocampal CA1 neurons to stimulation of the dopamine D-2 receptor.

Administration, Oral↗
PubMedDate not supplied

Prolonged administration of imipramine and (+)-oxaprotiline, but not citalopram, results in sensitization of the rat hippocampal CA1 neurons to serotonin ex vivo.

Prolonged (14 days, twice daily), but not acute, application of imipramine and (+)-oxaprotiline (10 mg/kg) induced sensitization of hippocampal CA1 neurons to the inhibitory effect of 5-hydroxytryptamine (5-HT), as studied ex vivo in the rat hippocampal slice preparation. Attenuation of the population spike, recorded in the CA1 pyramidal cell layer in response to stimulation of the Schaffer collateral-commisural pathway, was used to asses the sensitivity of neurons to 5-HT. Prolonged and acute administration of the selective 5-HT reuptake blocker citalopram did not change the responsiveness of hippocampal neurons to 5-HT. Since imipramine and (+)-oxaprotiline share the inhibitory effect on the norepinephrine reuptake, our results may indicate that long-term alterations in the noradrenergic system lead to modifications in postsynaptic serotonergic receptors.

Animals↗
PubMedDate not supplied

Multichannel stimulation of phrenic nerves by epineural electrodes. Clinical experience and future developments.

Between 1983 and 1992, 23 patients with complete ventilatory insufficiency of differing etiologies were treated with an eight channel implant (Medimplant Inc., Vienna) for fatigue free stimulation of both phrenic nerves. Data for 15 patients with high spinal cord lesions (ages: 9-51 years) are summarized: 1) level of lesion: C0, 3 patients; C1/C2, 4; C2/C3, 8; 2) time between incident and implantation: 3-14 months; 3) diaphragm training: 1-22 months; 4) chronic pacing: 5-83 months; 5) tracheostomy closed: 7 patients; 6) living permanently at home: 13 patients; 7) respiratory rate per minute: 12-17; 8) duration of inspiration: 1.0-1.3 sec; 9) tidal volume: 7-20 ml/kg body weight; 10) volume per minute: 121-198 ml/kg body weight; 11) pH: 7.39-7.42; 12) pCO2: 22.9-38.6 mmHg; 13) pO2: 81.2-104.5 mmHg; and 14) died by December 1992, 4 patients. All currently available implants for phrenic pacing need an external power supply and radio control. The authors have developed and tested the first fully implantable device. Features of this implant include an electronic circuit based on the microcontroller MC68HC705C8; surface mounted technology (SMD); eight channels; constant current source adjustable to 5 mA in 256 steps, impulse duration: 100-1000 musec, stimulation frequency: 1-33 Hz; and minimum lifetime: 3 years. The implant is programmed via bidirectional radio transmission using an IBM compatible computer. The dimensions, including battery, eight electrode connectors, and antenna, are 67 x 48 x 13 mm. The implant weights 58 g. This new device may improve patients' safety and quality of life in the near future.

Adolescent↗
PubMedDate not supplied

Effects of neuropeptide Y on evoked potentials in the CA1 region and the dentate gyrus of the rat hippocampal slice.

The effects of exogenously applied neuropeptide Y (NPY) on evoked field potentials in the CA1 area and dentate gyrus were examined in the in vitro hippocampal slice preparation from rate. The amplitudes of extra-cellularly recorded field potentials from the CA1 region were depressed by NPY (0.1-0.5 microM) in a dose-dependent manner. NPY had only little inhibitory effect in the area dentata. Similar effects were observed when synaptic excitation was recorded in the presence of the GABA(A) receptor antagonist picrotoxin. In the presence of picrotoxin, NPY reduced epileptiform discharges evoked in the disinhibited CA1 pyramidal cells suggesting that NPY may have antiepileptic action in this area. The effect of NPY on epileptiform discharges evoked in granule cells was minor. When NMDA-receptor mediated component of excitatory synaptic transmission was revealed in Mg2+ -free solution, NPY diminished both non-NMDA and NMDA receptor-mediated components of the field excitatory synaptic potentials recorded in the CA1 region. Such an effect is line with the reduction of glutamate release at the Schaffer collateral/commissural terminals by NPY.

2-Amino-5-phosphonovalerate↗
PubMedDate not supplied

MP-3022, a new putative antagonist at pre- and postsynaptic 5-HT1A receptors.

The receptor binding and pharmacological profile of the new, putative 5-HT1A receptor antagonist MP-3022 (4-[3-(benzotriazol-1-yl)propyl]-1-(2-methoxyphenyl)piperazine) were studied. Another 5-HT1A receptor antagonist, (S)-WAY 100135 ((S)-N-tert-butyl-3-[4-(2-methoxyphenyl)piperazine-1-yl]-2- phenylpropanamide), was used as a reference drug in functional models. MP-3022 showed a high affinity (Ki) of 25 nM and 69 nM, respectively, at 5-HT1A binding sites and alpha 1-adrenoceptors in vitro. The Ki values of MP-3022 in relation to other binding sites examined (5-HT2A, alpha 2- or beta-adrenoceptors, dopamine D1 and D2) were 20-100-fold lower. In functional studies, MP-3022 significantly attenuated the 8-OH-DPAT (8-hydroxy-2-(di-n-propylamino)tetralin)-induced decrease in the population spike evoked in the CA1 cell layer of the hippocampal slice preparation, without producing its own effects. The 8-OH-DPAT-evoked increase in the corticosterone concentration in the serum as well as the 8-OH-DPAT-mediated decrease in the 5-HT turnover in the hippocampus were attenuated by MP-3022. MP-3022 increased the serum corticosterone concentration only at the highest dose used, but it did not change the 5-HT turnover in the hippocampus. Like MP-3022, (S)-WAY 100135 antagonized the 8-OH-DPAT-induced effects. It has also been demonstrated that (S)-WAY 100135 is devoid of an intrinsic activity at 5-HT1A receptors. The data obtained demonstrate that, like (S)-WAY 100135, MP-3022 behaves like a functional antagonist at pre- and postsynaptic 5-HT1A receptors.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Antidepressant-induced adaptive changes in the effects of 5-HT, 5-HT1A and 5-HT4 agonists on the population spike recorded in hippocampal CA1 cells do not involve presynaptic effects on excitatory synaptic transmission.

Effects of repeated treatment with antidepressant drugs on the reactivity of CA1 neurons to 5-hydroxytryptamine (5-HT), (+/-)-8-hydroxy-2-(dipropyl-amino)-tetralin (8-OH-DPAT)--the 5-HT1A receptor agonist, and the zacopride-5-HT4 receptor agonist were examined in the rat hippocampus ex vivo. We sought to assess whether a presynaptic action of 5-HT receptor agonists on excitatory synaptic transmission contributed to the antidepressant-induced adaptive changes in responsiveness of pyramidal neurons to 5-HT1A and 5-HT4 receptor activation. The dendritic population excitatory postsynaptic potential (EPSP) evoked in the stratum radiatum of the CA1 region by stimulation of the Schaffer collateral-commissural pathway, was employed as a measure of the excitatory amino acid-mediated synaptic transmission, while the population spike recorded simultaneously in the CA1 cell layer was a measure of pyramidal cell excitability. 5-HT (10 microM) and 8-OH-DPAT (1 microM) decreased (by 40 +/- 5% and 30 +/- 7%, respectively), while zacopride (20 microM) increased (by 50 +/- 8%) the amplitude of the population spike. Neither drug had any effect on the slope of the population EPSP. The selective 5-HT1B receptor agonist CGS-12066 had no effect on the population spike or on the EPSP. Repeated treatment (14 days, twice daily, 10 mg/kg po) with imipramine and paroxetine augmented the inhibitory action of 5-HT on the population spike (by 50%), whereas treatment with citalopram and fluvoxamine had no effect. Imipramine and paroxetine, but not fluvoxamine, increased the 8-OH-DPAT-induced inhibition (by 80-100%). All of the antidepressant drugs studied attenuated the excitatory effect of zacopride on the population spike (by 70%). The population EPSPs in slices from rats treated with antidepressant drugs were not affected by 5-HT, 8-OH-DPAT or zacopride. It has been concluded that adaptive changes in the responsiveness of CA1 cells to 5-HT, 8-OH-DPAT and zacopride, induced by repeated administration of antidepressant drugs do not involve presynaptic effects on excitatory synaptic transmission.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMedDate not supplied

Imipramine-induced subsensitivity to the 5-HT4 receptor activation, a possible mediation via an alteration in the postreceptor transduction mechanism involving adenylate cyclase.

The effects of repeated treatment with imipramine on the reactivity of CA1 neurons in the rat hippocampus to the 5-HT4 receptor agonist zacopride and the direct adenylate cyclase activator forskolin were compared ex vivo to assess whether a modulation of signal transduction pathway may contribute to the antidepressant-induced adaptive changes in the responsiveness of pyramidal neurons to 5-HT4 receptor activation. The population spike recorded in the CA1 cell layer was a measure of pyramidal cell excitability, while the dendritic field excitatory postsynaptic potential (fEPSP) recorded in the stratum radiatum of the CA1 region was employed to assess the effects of the tested drugs on the excitatory amino-acid-mediated synaptic transmission. Zacopride (5 microM) and forskolin (1 microM) increased the amplitude of the half-maximal population spike (by 37 +/- 5% and 42 +/- 4%, respectively). Forskolin, but not zacopride, increased the slope of the fEPSP (by 13 +/- 2%). Repeated treatment with imipramine (14 days, twice daily, 10 mg/kg po) attenuated the excitatory effect of zacopride and forskolin on the population spike and the effect of forskolin on the fEPSP. It is concluded that the reduction in the responsiveness of CA1 cells to zacopride, induced by repeated administration of imipramine, may be due to modifications of the signal transduction pathway, i.e. adenylate cyclase and protein kinase A, which is responsible for the 5-HT4 receptor-mediated decrease in the activity of potassium channels.

Action Potentials↗
PubMedDate not supplied

Influence of imipramine treatment on the group I of metabotropic glutamate receptors in CA1 region of hippocampus.

Effects of repeated imipramine treatment on inositol phosphates accumulation and on the reactivity of neurons to metabotropic glutamate receptor (mGlu) agonist (1S,3R)-1-carboxycyclopentane-3acetic acid (1S,3R-ACPD) were investigated in the rat hippocampal slices. The concentration-dependent increase in inositol phosphate accumulation in the slices from CA1 region of hippocampus induced by 1S,3R-ACPD was not modified by imipramine treatment. 1S,3R-ACPD produced a concentration-dependent increase in population spike amplitude recorded in the CA1 cell layer. This effect of 1S,3R-ACPD was markedly attenuated by repeated imipramine administration. Our results indicate that antidepressant treatment may induce a subsensitivity of mGlu receptors in the CA1 region of hippocampus when estimated by electrophysiological, but not biochemical measures.

Animals↗