Biomedical subjects

M Bijak

Publications and source records attributed to M Bijak.

At least 55 records · Page 3Linked to original sources

PubMed1995

The effect of chronic treatment with imipramine on the responsiveness of hippocampal CA1 neurons to phenylephrine and serotonin in a chronic mild stress model of depression.

The effect of chronic mild stress (CMS) and chronic treatment with the tricyclic antidepressant drug imipramine (10 mg/kg/day for 5 weeks) on neuronal responsiveness to the alpha 1-noradrenergic agonist phenylephrine and serotonin (5-HT) was examined ex vivo, in the CA1 cell layer of the rat hippocampal slice preparation. We corroborated some previous findings that CMS, which had been used as an animal model of depression, decreased the consumption of a 1% sucrose solution and that that effect was reversed by chronic administration of imipramine. Imipramine did not change the sucrose consumption in control animals. In both control and stressed animals, phenylephrine (5 microM) and 5-HT (10 microM) attenuated the amplitude of the population spikes evoked in the CA1 pyramidal cell layer by stimulation of Schaffer collateral/commissural fibers. Those inhibitory effects of phenylephrine and 5-HT were significantly potentiated by chronic treatment with imipramine. The imipramine-induced potentiation was similar in slices from control and stressed animals. These results suggest that the imipramine-induced functional changes in alpha 1-noradrenergic and serotonergic receptors in the hippocampus are not involved in the anti-anhedonic effect of chronic imipramine administration in the CMS model of depression.

Animals↗

PubMed1995

Monitoring of FES-induced muscle activity by continuous EMG-recording.

Functional Electrical Stimulation (FES) requires information on the stimulated muscle for adjustment of the stimulation current, avoidance of muscle fatigue during the conditioning period and long term follow-up. Several applications of chronical FES are in clinical practice, but a system for direct registration of muscle activity under FES still does not exist. In six sheep the right Latissimus Dorsi Muscle (LDM) and Thoracodorsal Nerve were exposed. Stimulation electrodes were applied to each nerve and 3 EMG-applied sensing electrodes were placed into each LDM. The LDM tendon was connected to a force transducer. Burst stimulation was applied and the amplitude was increased from 0 to 4 mA in steps from burst to burst. EMG (M-wave) was amplified and recorded continuously via modified instrumentation amplifier, oscilloscope and tape recorder. Isometric muscle tension was recorded using force transducer, A/D interface and PC. Continuous EMG-recording was performed in all cases. Simultaneous recording of muscle tension and EMG revealed a close correlation (IrI=0.95, p < 0.0001) between the muscle strength and amplitude of the M-wave. Continuous recording of the EMG seems to be a reliable method for direct monitoring of the stimulated muscle. Three intramuscular electrodes can provide enough information to monitor FES induced muscle activity.

Animals↗

PubMed1994

Suppression by memantine and amantadine of synaptic excitation intrastriatally evoked in rat neostriatal slices.

The competitive N-methyl-D-aspartate (NMDA) receptor antagonists, DL-(E)-2-amino-4-methyl-5-phosphono-3-pentanoic acid (CGP 37849) and D(-)-2-amino-5-phosphonovaleric acid (APV), and the non-competitive NMDA antagonists, memantine and amantadine, which are used in the treatment of Parkinson's disease, were tested for their effects on intrastriatally evoked excitatory postsynaptic potentials (EPSPs) in rat neostriatal slices. Fast, non-NMDA receptor mediated synaptic excitation was not affected by any of the NMDA receptor antagonists. The NMDA component of the EPSPs was more prominent following reduction of the non-NMDA component of the EPSP by the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM). Memantine (30 microM) and amantadine (100 microM) had similar effects in reducing the NMDA component, but were not as effective as CGP 37849 (1-5 microM) or APV (10 microM). The data are compatible with a possible locus of action of memantine and amantadine in the neostriatum.

2-Amino-5-phosphonovalerate↗

PubMed1994

Differences in the Cs block of baclofen and 4-aminopyridine induced potassium currents of guinea pig CA3 neurons in vitro.

Single-electrode current- and voltage-clamp techniques were employed to study responses elicited by (-)baclofen or gamma-aminobutyric acid (GABA) and 4-aminopyridine (4-AP) induced inhibitory postsynaptic potentials in CA3 pyramidal neurons in guinea pig hippocampal slices. All drugs were applied by the bath to submerged slices in which fast synaptic transmission was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (10 microM), bicuculline (50 microM), and picrotoxin (50 microM). (-)Baclofen (0.5 microM) and GABA (1 mM) induced equivalent-sized hyperpolarizations and input resistance decreases. The agonist induced hyperpolarization or current and 4-AP induced hyperpolarizations or currents (4-AP induced K-IPSPs or IPSCs) reversed in sign near the K-equilibrium potential (EK). The GABAB receptor antagonists, OH-saclofen (500 microM) and CGP 35348 (100 microM), reduced (-)baclofen responses, and 4-AP induced K-IPSPs, suggesting that they were mediated by GABAB receptors. Intracellular tetraethylammonium-, and extracellular barium-ions (1 mM) diminished the (-)baclofen induced current and 4-AP induced K-IPSCs. Intracellular Cs-ions blocked the (-)baclofen induced outward current at resting membrane potential but did not grossly affect the inward current recorded at membrane potentials negative to EK. 4-AP induced inwardly or outwardly directed K-IPSCs were not blocked by intracellular Cs-ions. Extracellular Cs-ions (5 mM) blocked the (-)baclofen induced inward K-current, but did not block 4-AP induced inwardly directed K-IPSCs. In conclusion, we found differences in the Cs block of activated by (-)baclofen or the endogenous transmitter GABA.(ABSTRACT TRUNCATED AT 250 WORDS)

4-Aminopyridine↗

PubMed1993

Role of glutamatergic synaptic transmission in synchronized discharges of hilar neurons in guinea pig hippocampal slices.

The role of glutamatergic excitatory synaptic transmission in the synchronization of burst discharges in hilar neurons was studied using paired intracellular recording from hilar neurons and granule cells of guinea pig hippocampal slices. The convulsant 4-aminopyridine (4-AP, 50-100 microM) induced synchronous burst discharges in hilar neurons time locked to giant inhibitory postsynaptic potentials (IPSPs) in granule cells. The non-N-methyl-D-aspartic acid (non-NMDA) receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 5-10 microM) disrupted this synchrony. The inhibitory effect of gamma-aminobutyric acid (GABA)B receptor stimulation on the frequency of synchronous activity was smaller in the presence of CNQX than in its absence. We conclude that glutamatergic synapses operating through non-NMDA receptors are required for the synchronization but not for the generation of burst discharges which are induced by 4-AP in hilar neurons.

4-Aminopyridine↗

PubMed1993

CGP 55845A blocks baclofen, gamma-aminobutyric acid and inhibitory postsynaptic potassium currents in guinea pig CA3 neurons.

Single electrode voltage-clamp recording from CA3 neurons in guinea pig hippocampal slices was applied to study effects of a new GABAB antagonist, CGP 55845A, on (-)baclofen (IBac)- or gamma-aminobutyric acid (IGABA)-induced potassium (K)-currents and on inhibitory postsynaptic K-currents (K-IPSCs) recorded in the presence of blockers for fast synaptic transmission. K-IPSCs were induced by bath application of 4-amino-pyridine (4-AP). CGP 55845A, in 10(-8) to 10(-7) M concentrations, blocked all these K-currents and was more potent than all GABAB antagonists known to date. However, onset of the CGP 55845A effect and recovery were slow. We conclude that a potent and selective GABAB antagonist is now available to study the physiological role of GABAB receptors in the mammalian brain.

4-Aminopyridine↗

PubMed1992

K-dependent inhibition in the dentate-CA3 network of guinea pig hippocampal slices.

1. The occurrence of potassium-dependent inhibitory postsynaptic potentials (K-IPSPs) in relation to burst discharges induced by 4-aminopyridine (4-AP; 30 microM) was studied in CA3, granule and hilar neurons in guinea pig hippocampal slices with the use of paired extra- and/or intracellular recording. 2. Slow small (2-5 mV) and large (up to 30 mV) K-IPSPs were observed in CA3, granule and in some hilar neurons during 4-AP applications in the presence of blockers for fast synaptic transmission, picrotoxin (50 microM), and 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX; 5-10 microM). Amplitudes of K-IPSPs were linearly related to voltage, and they reversed in sign close to -100 mV, as expected for synaptic potentials generated by an increase in K-conductance. 3. In CA3 neurons, 4-AP applied in the presence of picrotoxin elicited burst discharges and K-IPSPs. CNQX blocked the burst discharge activity and increased the amplitude of K-IPSPs. 4. In granule cells, 4-AP applied in the presence of picrotoxin elicited K-IPSPs and only inconsistently small excitatory postsynaptic potentials (EPSPs). The EPSPs were blocked by CNQX, but CNQX application did not affect the K-IPSPs. However, in granule cells it could be observed that blockade of Cl-inhibition by picrotoxin in the presence of CNQX increased the amplitude of K-IPSPs. 5. In hilar neurons, 4-AP applied in the presence of picrotoxin elicited mainly burst discharges. CNQX blocked the burst discharges only in a few cells. In most hilar neurons K-IPSPs were observed at the beginning of the 4-AP effect, but subsequently K-IPSPs were replaced by burst discharges. 6. To determine the type of cells that burst in picrotoxin and 4-AP, neurons were stained intracellularly with horseradish peroxidase. Neurons stained in the granule cell layer did not burst and were morphologically identified as granule cells. Neurons stained in the hilar region burst and were nonpyramidal, nongranule cells. Bursting cells stained in the CA3 area were all pyramidal cells. 7. The hilar neurons varied considerably in size and dendritic organization. They could be classified as aspiny and spiny cells, the latter including mossy cells. 8. We conclude that K-dependent inhibition may explain the long-lasting IPSPs observed in in vivo recordings from hippocampal cells. In a hippocampal lamella, burst discharge activity of hilar neurons including presumed excitatory mossy cells is associated with inhibition of granule cells.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗

PubMed1992

Granule cell inhibition and the activity of hilar neurons.

Electrophysiological data from guinea pig hippocampal slices together with available morphological information about the dentate granule cell--hilar neuron circuitry strongly suggest that hilar neurons largely contribute to postsynaptic inhibition of granule cells. As in hippocampal pyramidal cells, inhibitory postsynaptic potentials in granule cells are either due to an increase in Cl-conductance or to an increase in K-conductance. It is therefore further suggested that hilar neurons inhibiting granule cells belong to at least two functionally distinct groups, those generating Cl-dependent and those generating K-dependent IPSPs. The presumed inhibitory action of hilar neurons is underlined by experiments applying pharmacological tools to suppress or enhance hilar neuron activity. Hyperpolarization of hilar neurons by the presumed GABAB-agonist (-)baclofen is associated with disinhibition of granule cells. If hilar neurons are activated by 4-amino-pyridine or picrotoxin to discharge in repetitive bursts, granule cells display repetitively occurring inhibitory postsynaptic potentials.

4-Aminopyridine↗

PubMed1991

Effects of antagonists on quisqualate and nicotinic receptor-mediated currents of midbrain neurones in culture.

1. The action of non-N-methyl-D-aspartate (non-NMDA) and nicotinic antagonists on excitatory postsynaptic currents (e.p.s.cs) and on quisqualate (Quis)- and nicotine-gated currents was studied by use of whole-cell recording in dissociated culture of the rat midbrain. 2. 6-Cyano-7-nitroquinoxaline-2,3-dione (CNQX; 0.1 microM) and kynurenic acid (0.1 mM) attenuated network-generated and miniature e.p.s.cs while mecamylamine (100 microM) and hexamethonium (400 microM) had no effect. Acetylcholine (ACh) enhanced or suppressed e.p.s.cs. The suppressing effect of ACh was blocked by atropine (0.1-10 microM). 3. ACh (50-1000 microM) and quisqualate (Quis, 0.1-20 microM) induced inward currents with the same reversal potential as e.p.s.cs. 4. Application of Quis and alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) in a low concentration (0.5 and 5 microM, respectively) evoked a maintained current which was attenuated by CNQX (1 microM) and kynurenic acid (0.5 mM) but not by mecamylamine (100 microM). 5. Higher concentrations of Quis (5-20 microM) and AMPA (50-100 microM) evoked a transient and a maintained current component. Kynurenic acid (1 mM) reduced the transient but not the maintained component. CNQX (5-10 microM) increased the maintained component without reducing the transient one; 20 microM CNQX reduced both components. 6. ACh-induced transient current was mimicked by nicotine and reversibly and dose-dependently blocked by mecamylamine. Atropine (10 microM), hexamethonium (400 microM) as well as CNQX (100 microM) and kynurenic acid (1 mM) did not affect the current. 7. Hexamethonium (50-400 microM) voltage-dependently depressed the maintained current elicited by both Quis and ACh. 8. In conclusion, although the antagonists examined here seem to discriminate between non-NMDA and nicotinic receptor-mediated e.p.s.cs, they vary considerably in respect of their mode of action when tested on Quis, AMPA and ACh-induced currents.

6-Cyano-7-nitroquinoxaline-2,3-dione↗

PubMed1990

Interaction of lithium with postsynaptic inhibition in guinea pig hippocampal neurons.

Intracellular recording techniques were used to study the effects of Li+ on postsynaptic inhibition of CA3 neurons in guinea pig hippocampal slices. Carbachol (0.3 microM) suppressed and phenylephrine (3 microM) enhanced the hyperpolarization induced by baclofen (0.15 microM). Low intracellular concentrations of Li+ (less than 10 microM) suppressed the muscarinic blockade of the K(+)-dependent inhibition, leaving its enhancement by noradrenergic receptor stimulation unchanged. K(+)-dependent inhibition per se was not affected. At high intracellular concentrations Li+ impaired postsynaptic Cl(-)-dependent inhibition by reducing the efficacy of an outward Cl- pump. While the effect of Li+ on the modulation of K(+)-dependent inhibition may be therapeutically relevant, its action on Cl(-)-dependent inhibition may underly some toxic effects.

Animals↗

PubMed1989

Antidepressant drugs potentiate the alpha 1-adrenoceptor effect in hippocampal slices.

The effect of prolonged treatment with antidepressant drugs on the phenylephrine- and norepinephrine (NE)-evoked reaction in hippocampal slices was examined by extracellular recording of the spontaneous activity of CA1 layer neurons. The alpha 1-adrenoceptor agonists, phenylephrine and methoxamine, depressed the neuronal discharges of most of the units tested, while NE evoked both excitatory and inhibitory effects which were blocked by propranolol and phentolamine or prazosin, respectively. Imipramine, mianserin, (+)- and (-)-oxaprotiline administered subchronically (10 mg/kg p.o., twice daily for 14 days, withdrawal 48 h), potentiated the inhibitory reaction to phenylephrine. Mianserin was the only drug tested in the acute dose to effectively augment the reaction to alpha 1-adrenoceptor stimulation. Prolonged administration of mianserin and imipramine attenuated the excitatory effect to NE, which probably reflects beta-receptor down-regulation; however, only mianserin, but not imipramine, enhanced the NE-induced inhibition. The observed potentiation of the alpha 1-adrenoceptor-related inhibitory reaction to phenylephrine produced by antidepressant drugs may reflect the development of the alpha 1-adrenergic system supersensitivity in the hippocampus.

Animals↗

PubMed1989

Serotonin receptor blocking effect of SCH 23390.

The effect of SCH 23390 administration on the serotonin system-dependent head twitch behavior was studied in the rat. A small dose of SCH 23390 (1.25 micrograms/kg), injected 20 min before the test, decreased the number of quipazine-induced head twitches. Repeated treatment with SCH 23390 (0.5 mg/kg, SC), once a day for 18 days, increased the number of spontaneously occurring and quipazine-induced head twitches. The enhancing effect of repeated administration of SCH 23390 was blocked by cyproheptadine (0.4 mg/kg). The results indicate that acute injection of SCH 23390 blocks central serotonin receptors, whereas repeated treatment induces their functional supersensitivity.

Animals↗

PubMed1989

Functional supersensitivity of the hippocampal dopaminergic system after prolonged treatment with haloperidol.

The effect of acute and prolonged (21 days) treatment with haloperidol (1 or 5 mg/kg SC) on the dopamine-, apomorphine- and LY 171555-induced changes in the firing rate of CA1 layer neurons was studied in a hippocampal slice preparation. Dopamine and apomorphine administration evoked either an excitatory or inhibitory reaction, while the selective D2 receptor agonist LY 171555 increased the firing rate of hippocampal neurons. The excitatory effects of dopamine and LY 171555 were blocked by sulpiride and haloperidol. Prolonged administration of haloperidol potentiated the excitatory reaction of dopamine and apomorphine; however, even a single dose of the neuroleptic enhanced the dopamine-induced effect. The reaction evoked by LY 171555 was not significantly affected by either acute or chronic treatment with haloperidol. The present findings indicate that long-term administration of haloperidol results in an increased sensitivity of hippocampal neurons to the mixed dopamine agonists, dopamine and apomorphine, but not to selective stimulation of the D2 receptor.

Animals↗

PubMed1989

Repeated administration of SCH 23390 enhances the SKF 38393-induced inhibition in the rat hippocampus.

The functional modification of the D1 dopamine receptor subtype following acute or repeated administration of the D1 receptor antagonist SCH 23390 (0.5 mg/kg s.c.) was studied in the rat hippocampal slice preparation. The activity of the D1 receptor system was evaluated by measuring the effect of the D1 receptor agonist SKF 38393 on the spontaneous firing of CA1 hippocampal neurons. The testing was performed 1, 2 and 7 days after discontinuation of the treatment. Repeated (21 days, once daily), but not acute, administration of SCH 23390 significantly potentiated the inhibitory reaction to SKF 38393. The inhibition evoked by SKF 38393 was blocked by application of SCH 23390 (10(-8) M). The results show that repeated treatment with SCH 23390 enhances the inhibitory effect of SKF 38393 in the rat hippocampus, probably due to an increase in the number of D1 dopamine receptors.

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

PubMed1989

Daily and seasonal variations in Na+, K+, Ca2+ and Mg2+ contents in the cingulate cortex of the mouse brain.

Daily changes in Na+, K+, Ca2+ and Mg2+ contents in the cingulate cortex of mice housed under controlled light/dark (LD) conditions were investigated for a 24-hour period in spring, summer, autumn and winter. The total ion content in the mineralized tissue was evaluated by absorption/emission flame spectrophotometry. In nearly all the tested cation contents significant daily concentration changes were found with a maximum in the dark phase of the LD cycle. The differences in wave form and mean cingulate cortex ion contents throughout the year suggest that the rhythms undergo seasonal variations. The functional importance of daily and anual fluctuations in the brain cation concentrations has been discussed.

Animals↗

PubMed1988

The effect of acute and prolonged treatment with citalopram on the action of dopamine and SKF 38393 in rat hippocampal slices.

The effect of acute and prolonged treatment with the 'atypical' antidepressant, citalopram, on the responsiveness of CA1 layer neurons to dopamine and SKF 38393 was studied in a hippocampal slice preparation from rat brain. Dopamine applied to slices prepared from non-treated rat brain evoked either an increase or a decrease in the spontaneous neuronal firing rate, while a selective D-1 receptor agonist, SKF 38393, and a selective D-2 receptor agonist, LY 171555, respectively evoked mainly an inhibitory and excitatory reaction. Both acute and repeated citalopram administration (10 mg/kg twice daily p.o.) were found to change the inhibitory action of SKF 38393 into excitation and to potentiate the excitatory reaction to SKF 38393. The latter effect of citalopram increased with time after drug withdrawal. Acute citalopram administration potentiated the excitatory effect of dopamine while chronic treatment with the drug increased the proportion of units reacting with excitation and significantly decreased the number of units which showed an inhibitory reaction. It is concluded that citalopram affects the dopaminergic system in the hippocampus by diminishing the incidence of the inhibitory reaction to dopamine agonists, this effect being related to D-1 dopamine receptors, and by potentiating the excitatory reaction related with D-2 dopamine receptor activation.

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

PubMed1988

Daily changes in the mouse cingulate cortex responsivity to neurotransmitters and depolarizing medium: an extracellular in vitro study.

1. The reaction of the mouse cingulate cortex neurons to the applied substances, measured as changes in the spontaneous activity, was investigated for daily variations in the in vitro slice preparation. 2. Glutamate- and GABA-evoked excitation and inhibition, respectively, were followed by long-lasting after-effects which showed greater potency in slices prepared in the evening. 3. Acetylcholine evoked excitation, inhibition and multiphasic effects. The incidence of an excitatory reaction prevailed in slices prepared in the evening. 4. The majority of cells studied in the evening were inhibited after application of a depolarizing medium, while in the morning the reaction was equally divided between excitation and inhibition. 5. The obtained results suggest that a day-night modulation is imposed upon the reactivity of the cingulate cortex neurons, and that daily changes in the reactivity are observed in vitro.

Acetylcholine↗

PubMed1987

Repeated treatment with imipramine enhances the excitatory response of hippocampal neurons to dopamine.

The effect of imipramine on the responsiveness of CA1 pyramidal neurons to dopamine was studied in hippocampal slices, obtained from rats treated acutely or repeatedly with imipramine (10 mg/kg, 14 days, twice a day p.o.). In slices from non-treated rats the bath-applied dopamine evoked mainly potentiation, while SKF 38393 produced diminution of the firing rate of hippocampal CA1 neurons. Acute imipramine did not significantly affect the reactiveness of neurons to dopamine, whereas repeated imipramine administration increased both the strength and duration of the response to dopamine. In animals pretreated both acutely and repeatedly with imipramine, SKF 38393 induced the excitatory, and not the inhibitory response, the obtained effect being more potent after repeated administration of imipramine. Haloperidol antagonized the excitatory reaction to dopamine but not to SKF 38393. SCH 23390 did not affect the excitation evoked by dopamine and SKF 38393. It is concluded that repeated imipramine administration induces supersensitivity of hippocampal dopamine D2 receptors in the rat which--in the light of our earlier studies--are responsible for the dopamine-evoked excitatory effect in the rat hippocampal slices.

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