Biomedical subjects

A Zahorodna

Publications and source records attributed to A Zahorodna.

9 recordsLinked to original sources

PubMed2006

Imipramine and citalopram reverse corticosterone-induced alterations in the effects of the activation of 5-HT(1A) and 5-HT(2) receptors in rat frontal cortex.

Using extracellular recording we studied changes in the reactivity of rat frontal cortical slices to the 5-HT(1A), 5-HT(2) and 5-HT(4) receptor agonists, (+/-)-2-dipropyloamino-8-hydroxy-1,2,3,4-tetrahydronaphtalene hydrobromide (8-OH-DPAT), (+/-)-2,5-dimethoxy-4-iodoamphetamine hydrochloride (DOI) and zacopride, respectively, induced by an earlier treatment of animals with corticosterone lasting 1 or 3 weeks. Spontaneous bursting activity was recorded in ex vivo slices incubated in a medium devoid of Mg(2+) ions and containing picrotoxin (30 microM). Repetitive, but not single, corticosterone administration resulted in an attenuation of the effect of the activation of 5-HT(1A) receptors and in an enhancement of the effect related to 5-HT(2) receptors. The effect of 5-HT(4) receptor activation remained unchanged. In separate two sets of experiments rats were treated with corticosterone for 3 weeks and additionally with imipramine or citalopram, beginning on the eighth day of corticosterone administration. In the corticosterone plus imipramine as well as corticosterone plus citalopram groups the effects of 8-OH-DPAT and DOI were not different from control indicating that corticosterone-induced functional modifications in the reactivity of 5-HT(1A) and 5-HT(2) receptors were reversed by antidepressant treatments.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2004

The influence of repeated administration of clozapine and haloperidol on the effects of the activation of 5-HT(1A), 5-HT(2) and 5-HT(4) receptors in rat frontal cortex.

The effects of a repeated treatment with antipsychotic drugs, clozapine and haloperidol, on the modulation of network activity ex vivo by 5-HT receptors were examined in rat frontal cortical slices using extracellular recording. Rats were treated for 21 days with clozapine (30 mg/kg p.o.), or haloperidol (1 mg/kg p.o.). Spontaneous bursting activity was induced in slices prepared 3 days after the last drug administration by perfusion with a medium devoid of Mg(2+) ions and with added picrotoxin (30 mM). The application of 2-3 microM 8-OH-DPAT, acting through 5-HT(1A) receptors, resulted in a reversible decrease of bursting frequency. In the presence of 1 microM DOI, the 5-HT(2) agonist, or 5 microM zacopride, the 5-HT(4) agonist, bursting frequency increased. Chronic clozapine treatment resulted in an attenuation of the effect of the activation of 5-HT(2) receptors, while the effects related to 5-HT(1A) and 5-HT(4) receptor activation were unchanged. Treatment with haloperiol did not influence the reactivity to the activation of any of the three 5-HT receptor subtypes. These data are consistent with earlier findings demonstrating a selective downregulation of 5-HT(2A) receptors by clozapine and indicate that chronic clozapine selectively attenuates the 5-HT-mediated excitation in neuronal circuitry of the frontal cortex while leaving the 5-HT-mediated inhibition intact.

Administration, Oral↗

PubMed2001

Opposite effects of antidepressants and corticosterone on the sensitivity of hippocampal CA1 neurons to 5-HT1A and 5-HT4 receptor activation.

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.

8-Hydroxy-2-(di-n-propylamino)tetralin↗

PubMed2001

Different receptor subtypes are involved in the serotonin-induced modulation of epileptiform activity in rat frontal cortex in vitro.

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.

Animals↗

PubMed2000

[Electrophysiologic tests for testing the effects of antidepressant drugs and corticosterone on reactivity of serotonin receptors in the hippocampus].

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.

Animals↗

PubMed1999

An antidepressant-induced decrease in the responsiveness of hippocampal neurons to group I metabotropic glutamate receptor activation.

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.

Animals↗

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↗