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Biomedical subjects

W Lasoń

Publications and source records attributed to W Lasoń.

At least 91 records · Page 5Linked to original sources
PubMedDate not supplied

Effects of estrogens on seizures and neurotoxicity.

Estrogens have proepileptic properties both in humans and experimental animals. On the other hand, estrogens attenuate neuronal damage due to a variety of insults including hypoglycemia, oxidative agents, hypoxia and glutamate receptor agonists. Since excitatory amino acids play a key role both in seizures and neurotoxicity, their involvement in the mechanism of proepileptic and neuroprotective effects of estrogens deserves special attention. In this short paper, some facts and hypotheses on genomic and nongenomic actions of estrogens on glutamate receptor-dependent seizures and neurotoxicity will be presented.

Animals↗
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Effects of some centrally active drugs on the allopregnanolone synthesis in rat brain.

Effects of antidepressants (desipramine, amitriptyline), anticonvulsants (phenytoin, diazepam, carbamazepine) and addictive drugs (amphetamine, morphine), used at a concentration of 100 microM on the conversion of [14C]-progesterone to 5alpha-pregnane-3,20-dione and allopregnanolone in slices of the frontal cortex and olfactory bulb from rat brain were studied. The synthesis of 5alpha-pregnane-3,20-dione and allopregnanolone was stronger in the olfactory bulb than in the frontal cortex. The biosynthesis of allopregnanolone in the frontal cortex was higher by 74, 109 and 187% when stimulated by amitriptyline, desipramine and carbamazepine, respectively, and, to a lesser degree, by phenytoin and morphine. Desipramine and morphine decreased the concentration of 5alpha-pregnane-3,20-dione. In the olfactory bulb, only carbamazepine enhanced allopregnanolone production, but none of the tested drugs had any effect on 5alpha-pregnane-3,20-dione synthesis. It is concluded that some psychotropic drugs may increase allopregnanolone synthesis by stimulating the activity of the enzyme, 3alpha-hydroxysteroid dehydrogenase, in the frontal cortex, and that this neurosteroid may be partly involved in the mechanism of action of the drugs under study.

5-alpha-Dihydroprogesterone↗
PubMedDate not supplied

Suppressive effect of TRH and imipramine on human interferon-gamma and interleukin-10 production in vitro.

It has been established that thyrotropin-releasing hormone (TRH) affects several aspects of immunoreactivity, e.g. production of pro-inflammatory cytokines, and enhances therapeutic efficiency of classic tricyclic antidepressants. On the other hand, it has been suggested that pro-inflammatory cytokines play a role in the etiology of depression, whereas the therapeutic efficacy of antidepressants is related to their negative immunoregulatory effect. In order to verify the hypothesis that the TRH-induced increase in the therapeutic efficiency of classic tricyclic antidepressants results from synergistic inhibitory effects of those two agents on the secretion of pro-inflammatory cytokines, we studied the effect of imipramine appliedjointly with TRH on the production of IFN-gamma and IL-10 by human whole blood cells stimulated in vitro by mitogens. A significant decrease in the production of IFN-gamma and IL-10 cytokines, by 36% and 34%, respectively, was observed in cells stimulated with mitogens and co-incubated with imipramine and TRH (either given at a dose of 10(-5) M). Under the same conditions, TRH alone did not change the production of those cytokines. Furthermore, imipramine alone decreased, not statistically significantly, though, the production of IFN-gamma. Hence our data only partly support the above-mentioned hypothesis, since TRH and imipramine applied jointly suppress the production of both the pro-inflammatory IFN-gamma and the anti-inflammatory IL-10 cytokines.

Adult↗
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Neurochemical and pharmacological aspects of cocaine-induced seizures.

Seizures associated with cocaine intoxication are serious clinical problem requiring immediate and adequate treatment, however their mechanism has not been fully elucidated. In contrast to early views, which convulsive properties of cocaine ascribed predominantly to the effect of this drug on voltage-dependent sodium channels, recent reports put much emphasis on the interaction of cocaine with GABAergic and glutamatergic systems. Accordingly, pharmacological studies demonstrated that cocaine-induced seizures were efficiently inhibited by GABA-A receptor agonists and NMDA receptor antagonists, whereas sodium and calcium channel blockers were ineffective. An involvement of serotonin 5-HT2, dopamine and sigma receptors in cocaine-induced seizures has also been proposed. Furthermore, adaptive changes in various neuronal systems following cocaine-induced seizures has been vigorously investigated. Some of those changes, such as expression of immediate early genes and increase in neuropeptide biosynthesis may play a compensatory anticonvulsive role, however, other alterations e.g. up-regulation of NMDA receptors may increase susceptibility to seizures. This short review summarises recent advances in basic research on some neurochemical and pharmacological aspects of cocaine-induced seizures.

Animals↗
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Immunoreactivity in kainate model of epilepsy.

Seizure-related changes in function of the peripheral immune system, especially in its cell component are poorly recognized. In the present study, we examined the effect of seizures induced by intraperitoneal injection of kainate to mice and rats on weight of central and secondary immunological organs and metabolic activity of splenocytes (MTT test). In kainate-injected mice the production of cytokines: interleukin 2 (IL-2) and IL-10 was also estimated. Seventy two hours after kainate administration, the mice and rats showed a marked decrease in the thymus weight by 36% and 50%, respectively, whereas the spleen weight tended to decrease in rats only. Splenocytes of kainate-injected mice and rats showed significant increase in metabolic activity. The ability of splenocytes of kainate-injected mice to produce IL-2 and IL-10 was reduced but only the former effect reached statistical significance. The results suggest a decrease in T helper-cell dependent immunoreactivity and enhanced phagocytic activity of macrophages in kainate-treated rodents.

Animals↗
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Effect of topiramate on the kainate-induced status epilepticus, lipid peroxidation and immunoreactivity of rats.

Topiramate, a new anticonvulsant, has been reported to possess neuroprotective effects in both in vivo and in vitro experiments. In the present study, the effect of topiramate (40 and 80 mg/kg ip) on the fully developed kainate-induced status epilepticus was evaluated in the rat. Injection of kainate (15 mg/kg ip) evoked recurrent limbic seizures which lasted several hours. Topiramate injected 1.5 h after kainate administration had no effect on the seizures and mortality of the animals. Biochemical study revealed that at 80 mg/kg ip, topiramate significantly attenuated the kainate-induced lipid peroxidation in the piriform cortex and showed similar tendency in the frontal cortex. Besides the central nervous system, the kainate-induced seizures evoked significant changes in immunoreactivity, such as reduction in thymus weight and the proliferative activity of splenocytes, and the splenocyte-increased production of interleukin-10, but not interferon-gamma. Topiramate did not affect the kainate-induced reduction in thymus weight, but attenuated changes in the proliferative activity of splenocytes. It is concluded that topiramate, when given during the fully developed kainate-induced status epilepticus in rats, has no effect on seizures, but attenuates lipid peroxidation in piriform cortex and prevents certain changes in immunoactivity.

Animals↗
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The effects of ethanol treatment on endogenous opioid peptides level and analgesia in monoarthritic rats.

The effect of acute and repeated exposure to ethanol on endogenous opioid peptides level in rats was studied. Acute ethanol administration decreased beta-endorphin level in hypothalamus and anterior lobe of pituitary as well as alpha-neoendorphin in the spinal cord. In contrast, repeated ethanol treatment increased hypothalamic beta-endorphin content and did not affect the peptide level in the pituitary. No changes in alpha-neoendorphin and dynorphin level after repeated ethanol administration were observed. Exposure of rats to long-term noxious stimuli by means of induction of monoarthritis prevented the increase in hypothalamic beta-endorphin level by repeated ethanol treatment. As measured by tail-flick test only the first two administrations of ethanol resulted in analgesia. Further administration of increasing doses of ethanol did not affect the pain threshold. Altered response of endogenous opioid systems to repeated ethanol treatment as compared with effects of its acute administration may suggest involvement of these systems in development of tolerance to ethanol.

Administration, Oral↗
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Stress prevents the chronic ethanol-induced delta opiod receptor supersensitivity in the rat brain.

The effects of ethanol administration on binding characteristics of the highly selective mu and delta opioid receptor agonists 8H-[D-Ala2-MePhe4-Gly5-ol]enkephalin (3H-DAGO) and 3H-[D-Pen2, D-Pen5] enkephalin (3H-DPDPE), respectively, were investigated in the rat brain. Chronic but not acute ethanol administration profoundly increased affinity of 3H-DPDPE without changing the number of delta receptors. Stress, applied before each ethanol administration, prevents the above changes. On the other hand, chronic treatment with ethanol did not affect the binding characteristics of 3H-DAGO. These results suggest particular sensitivity of the delta opioid receptor to chronic ethanol administration. Furthermore, a possible involvement of endogenous opioid peptide systems in the enhancement of delta opioid receptor sensitivity is postulated.

Analgesics↗
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Serotonergic regulation of the brain and gut beta-endorphin and dynorphin content in the rat.

A specific radioimmunoassay was used to measure immunoreactive dynorphin (ir-DYN) and beta-endorphin (ir-BE) in the brain, pituitary and gut, following a pharmacological manipulation of the serotonin system. Administration of the serotonin receptor agonist m-chlorophenylpiperazine (m-CPP, 2.5-5 mg/kg ip) or the serotonin releasing agent fenfluramine (20-40 mg/kg ip) induced a significant increase in the hypothalamic ir-BE content and a decrease in its anterior pituitary level. These effects were antagonized by cyproheptadine (1 mg/kg ip). Similar results were obtained after fluvoxamine (15 mg/kg ip), femoxetine (10 mg/kg ip) and 5-hydroxytryptophan (5-HTP 40-160 mg/kg ip). None of the above treatments altered significantly the ir-DYN content in the brain and pituitary. However, the gut ir-DYN level was dramatically decreased after m-CPP, fenfluramine, fluvoxamine, femoxetine and 5-HTP. The latter effect was antagonized by cyproheptadine. The obtained results suggest that serotonergic activation stimulates the release of beta-endorphin from the anterior pituitary and dynorphin from the gut, while the cerebral beta-endorphin system appears to be inhibited by activation of serotonin neurons.

Animals↗
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The difference in stress-induced analgesia in C57BL/6 and DBA/2 mice: a search for biochemical correlates.

The level of opioid peptides: beta-endorphin and dynorphin, binding to the mu and kappa opioid receptors and the analgesic response of those endogenous opioid systems to stress were investigated in two strains of mice: C57BL/6 (C57) and DBA/2 (DBA). The nociceptive threshold of DBA mice was higher than that of C57 mice. KD values for spinal mu receptors were lower in C57, while KD for cerebral kappa receptors were higher in this strain. DBA mice have significantly higher concentrations of dynorphin in the hypothalamus and neurointermediate lobe of the pituitary. Stress-induced analgesia was much greater in C57 than in DBA mice. In the hypothalamus both stress procedures depressed the concentrations of beta-endorphin in C57, and dynorphin in DBA mice. The level of beta-endorphin increased in the neurointermediate lobe in C57 and in anterior lobe of the pituitary in DBA mice. In the spinal cord both stress procedures depressed the dynorphin level. The above data indicate that C57 and DBA mice differ in the endogenous opioid peptide content, stress-induced alteration and opioid receptor affinity, the effects which might correlate with their different responses to environmental factors and pharmacological agents.

Analgesia↗
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Degradation of the labelled beta-endorphin is an important factor of direct RIA in the human and rat plasma.

Degradation of iodinated beta-endorphin in human and rat plasma was investigated, using different proteinase inhibitors. This degradation affects the radioimmunoassay quality. Additional blank tubes were also prepared during assay procedure to avoid the effect of 125-I-beta-endorphin adsorption on the dextran-coated charcoal in the presence and absence of plasma proteins, what avoids underestimation of the beta-endorphin level in plasma samples. Based on the above observations, the sensitive and direct radioimmunoassay of beta-endorphin was developed in human and rat plasma.

Animals↗
PubMedDate not supplied

The difference in the tail-flick latency between C57BL/6 and DBA/2J mice.

The tail-flick latency, measured using radiant heat as a noxious stimulus, was significantly shorter in C57BL/6 than in DBA/2J mice, while no significant interstrain differences were observed in the hot-plate test. The experiments in which the animals' tail was painted indicated that the difference in the tail-flick latency between strains was caused by the difference in the color of animal's coat.

Animals↗
PubMedDate not supplied

Repeated amphetamine evokes long-lasting depletion of thyrotropin-releasing hormone in the rat adrenal medulla.

Long-term amphetamine administration (5 mg/kg, ip, twice a day for 14 days) profoundly decreased the TRH level in the rat adrenal medulla at 2 h (by ca. 76%), 24 h (by ca. 51%) and 72 h (by ca. 48%) after the last drug injection. Single amphetamine (5 mg/kg ip) had no significant effect on the TRH level in that tissue, as measured at 2 h after the drug injection. Since TRH in the adrenal medulla is thought to exert a paracrine, inhibitory influence on the adrenal cortex, depletion of the peptide content may contribute to a persistent elevation of the plasma corticosterone level following repeated treatment with amphetamine.

Adrenal Medulla↗
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Pharmacological modulation of glucocorticoid and mineralocorticoid receptors in the rat central nervous system.

This review examines neurochemical mechanisms of the corticosteroid receptor regulation in the central nervous system. Glucocorticoid (GRs) and mineralocorticoid (MRs) receptors are localized in discrete brain regions, especially in the limbic system, and exert inhibitory control over the hypothalamic-pituitary-adrenal (HPA) axis; moreover, they are found to affect the responsiveness of neurotransmitters. The GR and MR levels and biosynthesis appear to be under a serotoninergic and, to a lesser extent, a noradrenergic, cholinergic and dopaminergic influence. Of the neuropeptides studied, vasopressin and ACTH regulate the corticosteroid receptor density. The above data strongly suggest that GR and MR may be affected by some psychotropic drugs which are known to cause alterations in classic neurotransmitter systems. In this respect, adaptive changes in GR and MR parameters, evoked by drugs which are commonly administered for a long time, e.g. antidepressants or drugs of abuse, seem to be of particular interest. Long-term treatment with tricyclic antidepressants such as imipramine, desipramine, amitriptyline and maprotiline elevates the density and/or biosynthesis of GR and/or MR. Similar effects are observed after chronic lithium or repeated electroconvulsive shock (ECS), which suggests that alterations in corticosteroid receptors may be involved in the mechanism of their antidepressant action. On the other hand, chronic administration of drugs of abuse, such as amphetamines or morphine, down-regulates GR which may impair the feedback control mechanism of the HPA activity.

Animals↗
PubMedDate not supplied

The effect of chronic treatment with imipramine on the G proteins mRNA level in the rat hippocampus--an interaction with a calcium channel antagonist.

The effect of long-term administration of imipramine (10 mg/kg po, twice daily, 30 days) with or without nifedipine (5 mg/kg ip, twice daily, 28 days) on the G protein alpha subunit, Gs alpha, Go alpha and Gi alpha mRNA levels was investigated in the rat hippocampus. An in situ hybridization histochemistry showed that imipramine decreased the Go alpha mRNA level in CA1 (by ca. 40%) and CA3 (by ca. 37%) hippocampal fields and, to a lesser extent, in the dentate gyrus (by ca. 25%), but had no effect on the Gs alpha and Gi alpha mRNA levels in those structures. Nifedipine decreased (by ca. 30%) the Gs alpha level in the studied fields of hippocampal formation, having no influence on the level of mRNA which codes other subunits of G protein. Coadministration of nifedipine and imipramine reversed the imipramine effect on Go alpha, but had no effect on the nifedipine-induced decrease at the Gs alpha mRNA level. These results suggest that inhibition of L calcium channels modifies the effect of imipramine at the level of intracellular signal transduction.

Animals↗
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Repeated amphetamine administration down-regulates glucocorticoid, but not mineralocorticoid, receptors in the rat hippocampus.

It has been postulated that activation of the hypothalamic-pituitary-adrenal (HPA) axis is critical to the development of sensitization to amphetamine. Since this axis is under inhibitory control of hippocampal corticosteroid receptors, the present study has been designed to determine the effects of repeated (5 mg/kg, ip, twice a day for 14 days) d-amphetamine (AMPH) administration on binding parameters of these receptors. Glucocorticoid (GR) and mineralocorticoid (MR) receptors were examined by an in vitro [3H]corticosterone binding in the cytosol from the rat hippocampus, using the selective GR agonist RU 28362 to discriminate between MR and GR. Repeated, but not single, treatment with AMPH significantly reduced the density of GR (decrease by ca. 20%). The density of MR tended to decrease 2 h, but not 72 h, after the last drug injection. No changes in dissociation constants were found following single or repeated AMPH administration. The plasma corticosterone level was significantly increased 1, 2 and 72 h after chronic administration of AMPH. Obtained results indicate that repeated AMPH administration down-regulates GR receptors and increases plasma corticosterone level. These changes may reflect neurochemical mechanism of addictive properties of AMPH.

Adrenalectomy↗
PubMedDate not supplied

Repeated cocaine administration down-regulates glucocorticoid receptors in the rat brain cortex and hippocampus.

Chronic exposure to psychostimulants results in an aberrant activity of the hypothalamic-pituitary-adrenal (HPA) axis. Since this axis is under inhibitory control of corticosteroid receptors, the present study has been designed to determine the effects of repeated (15 mg/kg, ip, once an hour for 3 h, for 8 days) cocaine administration on cytosolic and nuclear glucocorticosteroid receptor (GR) levels in the hippocampus and frontal cortex of the rat. As shown by a sensitive Western blotting technique, repeated (but not single) treatment with cocaine significantly reduced the density of cytosolic GR in the frontal cortex (by ca. 23%) and to a lesser extent in the hippocampus (by ca. 10%), after 45 min and 72 h, respectively. No changes in the nuclear fraction of the GR level were found following repeated cocaine administration, whereas acute treatment enhanced the signal in the hippocampus by ca. 17%. The obtained results indicate that repeated cocaine administration decreases the level of GR in the cytosol, but does not enhance transport of these receptors into the nuclei. The down-regulation of cortical and hippocampal GR receptors may play some role in the cocaine-induced impairment of the feedback control mechanism of the HPA axis activity.

Analysis of Variance↗