Biomedical subjects

W Lasoń

Publications and source records attributed to W Lasoń.

At least 55 records · Page 3Linked to original sources

PubMed1995

Seizure related changes in the regulation of opioid genes and transcription factors in the dentate gyrus of rat hippocampus.

An in situ hybridization study showed that limbic seizures induced by kainate strongly augmented the prodynorphin and proenkephalin messenger RNA levels in granular cells of the rat hippocampal dentate gyrus. Pentylenetetrazole increased the level of proenkephalin messenger RNA, but slightly decreased that of prodynorphin messenger RNA in the dentate gyrus. Administration of kainate to rats caused a profound increase in messenger RNAs of the transcription factor genes c-fos and c-jun in the dentate gyrus, followed by an increase in the level of the transcriptional complex activator protein-1 in hippocampal neurons. Pentylenetetrazole also elevated the formation of activator protein-1, but the effect appeared earlier than that induced by kainate. Thus, recurrent limbic seizures activate both prodynorphin and proenkephalin genes, whereas generalized clonic-tonic seizures seem to decrease the prodynorphin and increase the proenkephalin gene expression in the dentate gyrus. Furthermore, our present results suggest that the transcription factors, c-fos, c-jun and activator protein-1 complex may be involved in the process of inducing the hippocampal proenkephalin gene, while these factors might be differently involved in regulation of prodynorphin gene expression.

Animals↗

PubMed1995

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

Activation of the hypothalamic-pituitary-adrenal axis (HPA) is known to be an important component of a neuroendocrine response to opiates. Since this axis is under inhibitory control of hippocampal corticosteroid receptors, the present study has been designed to determine the effects of single (20 mg/kg IP) and repeated (from 20 to 100 mg/kg/day, IP, twice a day for 10 days) morphine 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 morphine significantly (by approximately 22%) reduced the density of GR at 2 h and tended to decrease it at 72 h after the last drug injection. The density of MR was unchanged at those time points. No changes in dissociation constants of either type of the receptors were found following single or repeated morphine administration. The plasma corticosterone level was significantly increased 1 h after acute and chronic administration of morphine (382 and 527%, respectively). These results indicate that repeated morphine administration downregulates GR receptors, which may impair the feedback control mechanism of the HPA activity.

Animals↗

PubMed1995

Adaptive changes in the proenkephalin and D2 dopamine receptor mRNA expression after chronic cocaine in the nucleus accumbens and striatum of the rat.

The effects of single and repeated cocaine administration on proenkephalin (PENK) and D2 dopamine receptor mRNA expression in the nucleus accumbens and striatum of the rat were studied. Acute cocaine administration increased PENK expression of mRNA in the striatum and decreased it in both those structures after 24 and 48 h. D2 receptor expression of mRNA fell after 3 h, returned to the control value after 24 h and rose after 48 h in both those brain regions following single cocaine injection. Repeated cocaine increased PENK expression of mRNA after 3 h, but after 24 and 48 h depletion of mRNA expression was observed. On the other hand, a decrease in the D2 expression of mRNA was found after 3 h in those structures, but no changes were found after 24 and 48 h following withdrawal. The obtained results suggest that in the nucleus accumbens and striatum there is an opposite regulation between PENK and D2 receptor gene expression a short time after single and chronic cocaine administration. Hence, these data provide further evidence for the significance of the PENK and dopamine systems in the neurochemical mechanism of cocaine.

Adaptation, Physiological↗

PubMed1994

The effects of cocaine-induced seizures on the proenkephalin mRNA level in the mouse hippocampus: a possible involvement of the nitric oxide pathway.

The effect of the nitric oxide synthase inhibitor L-NG-nitroarginine methyl ester (L-NAME, 2 and 10 mg/kg i.p.) on behavioral and biochemical changes induced by single and repeated administration of cocaine (45 mg/kg/day, i.p., for 5 days) was investigated in mice. Repeated cocaine produced a progressive increase in the intensity of seizures (a ca. 300% increase in the seizure score on day 5, as compared to day 1), this effect being associated with the enhancement of the proenkephalin mRNA level (ca. 240%) in the hippocampal dentate gyrus. L-NAME had no influence, but when used jointly with cocaine, it markedly attenuated both behavioral and biochemical effects of repeated cocaine. These data suggest that the nitric oxide pathway is involved in the progressive increase in excitability of the central nervous system after repeated cocaine administration.

Animals↗

PubMed1994

Repeated amphetamine evokes biphasic alterations in the tyrosine hydroxylase mRNA level in the rat adrenal medulla: an in situ hybridization study.

In the present study we estimated the effects of single and repeated administration of d-amphetamine (5 mg/kg, i.p., twice a day for 14 days) on tyrosine hydroxylase (TH) mRNA levels in the rat adrenal medulla. In situ hybridization experiments, conducted using a [35S]d-ATP-labelled deoxyoligonucleotide probe and a densitometric analysis of autoradiograms, showed that repeated d-amphetamine moderately increased the TH mRNA level (by ca. 24%) in the adrenal medulla at 2 h after the last injection. In contrast, after 48 h the TH mRNA level was decreased (by ca. 21%). No significant changes in the TH mRNA level in the adrenal medulla were found following single administration of d-amphetamine. These results suggest that repeated d-amphetamine administration leads to biphasic changes in the adrenal TH biosynthesis, which may reflect an adaptive response to chronic drug treatment.

Adrenal Medulla↗

PubMed1994

Effects of mu and delta opioid receptor agonists and antagonists on absence epilepsy in WAG/Rij rats.

The effects of various types of opioid receptor agonists and antagonists were determined in a genetic rat model for generalized absence epilepsy. Rats of the WAG/Rij strain spontaneously showed several hundred spike-wave discharges per day. Intracerebroventricular (i.c.v.) injections of the selective mu agonist DAMGO (0.2, 0.7 microgram) resulted in a dose-related increase in the number of spike-wave discharges, while the selective delta agonist DPDPE (20, 60 micrograms) was without effect. DAMGO reduced the duration of automatic behavior, enhanced the immobile behavior (after the low dose) and had no effect on exploratory behavior. On the other hand, DPDPE significantly enhanced the total time spent on exploration, but did not influence other behavioral parameters. There was no correlation between the ability to the drug to modulate the epileptic activity and behavioral changes. The nonselective antagonist naloxone, administered either i.p. (0.4, 2.0, 10 mg/kg) or i.c.v. (10, 50 micrograms), increased the number of spike-wave discharges in a dose-dependent way. The specific delta receptor antagonist naltrindole (0.3, 1 mg/kg) was without effect, as was the irreversible mu receptor antagonist beta-funaltrexamine (beta-FNA). Pretreatment with beta-FNA diminished the action of DAMGO. These results clearly indicate that activation of the mu opioid receptor increases the number of spike-wave discharges, and that modulation of delta receptors is not effective. On the other hand, the naloxone-induced enhancement of spike-wave discharges, suggests a tonic control of the epileptic activity by another opioid system. These results point to an important role of the mu-, but not delta-, receptor in facilitation of the epileptic activity in WAG/Rij rats.

Analysis of Variance↗

PubMed1994

Proenkephalin and prodynorphin mRNA level in brain of rats with absence epilepsy.

An in situ hybridization method was used to estimate the proenkephalin (PENK) and prodynorphin (PDYN) mRNA levels in the brain of epileptic 6-month-old WAG/Rij rats in comparison with non-epileptic: 3-month-old WAG/Rij rats, 3-month-old ACI rats and 6-month-old ACI rats. The epileptic rats had a significantly higher level of PENK mRNA in the striatum as compared to non-epileptic controls. The PDYN mRNA level was significantly elevated only in the hippocampus of epileptic rats, whereas age- or strain-related changes in the striatal and cortical PDYN mRNA levels were found in both epileptic and non-epileptic rats. The changes in the biosynthetic activity of endogenous opioid peptide systems may be important for the occurrence of epileptic discharges in these animals.

Aging↗

PubMed1994

Seizure-induced expression of G proteins in the rat hippocampus.

The effects of kainic acid (15 mg/kg i.p.) on alpha subunits of the Gs and Go protein mRNA levels in the rat hippocampal formation were investigated. An in situ hybridization study showed an increase in the Gs alpha mRNA level in the dentate gyrus at 3 h (by ca. 17%), 24 h (by ca. 75%), 72 h (by ca. 89%) and 30 days (by ca. 59%) after kainic acid administration. An emulsion autoradiography revealed enhancement in the Gs alpha mRNA signal intensity over granular cells of the dentate gyrus and over some hilar cells adjacent to the granule cell layer, most likely in GABA interneurons. The Gs alpha mRNA showed a slight tendency to increase in the CA1 and CA3 pyramidal cell layers at 3 h after kainic acid administration, but it decreased after 24 h, 72 h and 30 days. The latter decrease correlated well with the pyramidal cells loss in those areas. Kainic acid differently influenced the Go alpha mRNA level in the dentate gyrus: it had no effect after 3 h, while after 24 h the mRNA level tended to decrease (by ca. 16%); then it increased after 72 h (by ca. 20%) and, to a lesser extent, after 30 days (by ca. 12%). The Go alpha mRNA level in CA1 and CA3 tended to decrease at 3 h after kainic acid administration; the signal completely disappeared after 24, 72 h as well as after 30 days.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effect of chronic morphine and cocaine administration on the Gs and Go protein messenger RNA levels in the rat hippocampus.

The effects of single (20 or 50 mg/kg) and repeated morphine (14 days, rising doses: four days, 2 x 10 mg/kg; two days, 2 x 20 mg/kg; two days, 2 x 30 mg/kg; two days, 2 x 40 mg/kg and four days, 2 x 50 mg/kg i.p.) or cocaine (20 mg/kg i.p., once every hour for 3 h for one or five days) on the Gs alpha and Go alpha protein messenger RNA levels were investigated in the rat hippocampus. As shown by in situ hybridization immunocytochemistry and optical densitometry of autoradiograms, acute morphine (20 mg/kg) decreased the Gs alpha messenger RNA level and increased the Go alpha messenger RNA level in the dentate gyrus and CA1 hippocampal region. Repeated morphine administration significantly decreased the hippocampal Gs alpha messenger RNA level at 12, 24 and 48 h, and enhanced the Go alpha messenger RNA level in those areas at 12 and 24 h after the last injection. Repeated and acute cocaine administration decreased the Go alpha messenger RNA level in the CA3 region and increased it in the CA1 at various time points. Furthermore, in all hippocampal regions, acute, but not chronic, cocaine administration increased the Gs alpha mRNA level at 24 h, whereas chronic treatment significantly decreased that level at 48 h after the last dose. The data indicate that chronic morphine elevates the Go and attenuates the Gs protein biosynthesis at later time points in all regions of the hippocampal formation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

The effect of repeated amphetamine administration on the proopiomelanocortin mRNA level in the rat pituitary: an in situ hybridization study.

The effect of single and repeated administration of amphetamine (5 mg/kg i.p., twice daily, 14 days) on the proopiomelanocortin (POMC) mRNA level was investigated in the rat pituitary. In situ hybridization histochemistry, using a 35S-d-ATP-labelled deoxyoligonucleotide probe and densitometric analysis of autoradiograms, showed that repeated administration of amphetamine moderately increased the POMC mRNA level (by approximately 16%) in the anterior and the intermediate lobes of the pituitary at 72, but not 2, hr after the last injection. Adrenalectomy (48 h after the last drug injection) increased the POMC mRNA level only in the anterior lobe of repeated saline- and amphetamine-treated rats by 59 and 67%, respectively. No significant changes in POMC mRNA level in either lobe were found following single administration of amphetamine. These results suggest that repeated amphetamine administration leads to a delayed and moderate increase in POMC biosynthesis in the rat pituitary. On the other hand, the responsiveness of the POMC pituitary system to adrenalectomy was not significantly altered in rats treated repeatedly with amphetamine.

Adrenalectomy↗

PubMed1994

Kappa opioid receptor agonists inhibit the pilocarpine-induced seizures and toxicity in the mouse.

Involvement of the kappa opioid receptor in regulation of the pilocarpine-induced seizures and neurodegeneration was studied in mice. Administration of pilocarpine (400 mg/kg i.p.) resulted in a sequence of behavioral alterations including motor limbic seizures. Pretreatment of mice with the selective kappa opioid receptor agonist U69,593 (2 and 20 mg/kg i.p.) or PD117,302 (0.1 and 1 mg/kg i.p.) increased the latency of motor seizures and decreased the seizure severity and mortality. Those effects were abolished in animals pretreated with the specific kappa opioid receptor antagonist nor-binaltorphimine (Nor-BNI, 10 mg/kg i.p.). Examination of frontal forebrain sections by light microscopy revealed widespread damage, especially within the hippocampal formation, in pilocarpine-treated mice. Both U69,593 and PD117,503 protected the integrity of hippocampal neurons, especially in the CA1 region, that effect being reversed by Nor-BNI. The above data indicate that activation of the kappa opioid receptor exerts an inhibitory effect on the pilocarpine-induced limbic seizures and neurotoxicity.

Analgesics↗

PubMed1994

Repeated ethanol differently affects opioid peptide biosynthesis in the rat pituitary.

In situ hybridization and specific radioimmunoassays were used to study the influence of ethanol on proopiomelanocortin (POMC) and prodynorphin (PDYN) biosynthesis in the rat pituitary. Repeated intragastric ethanol administration (starting with a total daily dose of 5 g/kg every 2nd day, until a dose of 10 g/kg was attained on the 10th day and that dose was maintained by the 19th day) resulted in a reduction in the POMC mRNA level (about 20%) in the intermediate lobe of the pituitary (3 h after the last dose), whereas the level of beta-endorphin in the neurointermediate lobe was attenuated (by about 32%) only during the withdrawal (48 h after the last dose). Additionally, the plasma level of beta-endorphin after repeated ethanol and during withdrawal was significantly reduced (by about 44 and 66%, respectively). No changes in the POMC mRNA or the beta-endorphin levels were detected in the anterior lobe. In contrast, the PDYN mRNA level was found to be decreased in the anterior lobe during the withdrawal (by about 43%). This decrease was in conjunction with an increase in the alpha-neoendorphin level (by about 57%) in that lobe. The PDYN mRNA level in the intermediate lobe and the alpha-neoendorphin level in the neurointermediate lobe were unchanged after ethanol, as well as during the withdrawal period. Acute ethanol (5 g/kg) decreased the level of beta-endorphin in the anterior lobe; this effect being associated with an elevation in the peptide level in plasma. On the other hand, acute ethanol had no effect on the POMC and PDYN mRNA levels, nor did it affect the alpha-neoendorphin concentration in the pituitary.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Repeated ethanol administration decreases prodynorphin biosynthesis in the rat hippocampus.

The effect of single and repeated (19 days) intragastric ethanol administration on prodynorphin mRNA and alpha-neoendorphin levels in the hippocampus of the rat was studied using in situ hybridization and RIA methods, respectively. Single ethanol administration had no effect on either of these two parameters. Repeated ethanol administration decreased both immunoreactive (ir) alpha-neoendorphin (by ca. 37%) and prodynorphin mRNA (by ca. 57%) levels. Two days after the last dose of ethanol no changes in the ir-alpha-neoendorphin tissue content were found, whereas the level of prodynorphin mRNA remained decreased (by ca. 44%). These results suggest that repeated ethanol evokes a long-lasting decrease in the biosynthesis of hippocampal prodynorphin, this effect that may play some role in the ethanol-induced deficiency of neuronal functions.

Alcoholism↗

PubMed1992

Differential effects of opioid receptor agonists on nociception and cAMP level in the spinal cord of monoarthritic rats.

Changes in functional responsiveness of spinal opioid receptors in monoarthritic rats were investigated at the behavioral and the molecular level. After intrathecal administration of morphine, D-Ala2-D-Leu5-enkephalin (DADLE), D-Pen2-D-Pen5-enkephalin (DPDPE) and dynorphin monoarthritic rats showed an enhanced antinociceptive response as measured by a tail-flick latency. No such changes were observed following administration of the selective kappa agonists U50,488H and U69,593. The opioid mu and delta receptor agonists (0.1-1.0 microM) inhibited the basal, as well as the forskolin-stimulated cAMP formation in spinal cord slices obtained from monoarthritic rats, whereas no significant changes were found in control animals. Higher concentrations of the mu and delta opioid receptor agonists were required to attenuate the cAMP level in spinal cord of control animals. The selective kappa agonists U50,488H and U69,593 did not influence the cAMP formation in monoarthritic or control animals. Additionally, we found that the GppNHp-stimulated level of cAMP was higher in the spinal cord slices of monoarthritic rats, which points to an enhanced responsiveness of the adenylate cyclase effector system to the action of this GTP analog. Our data suggest that the enhanced antinociceptive response to intrathecally administered opioids in monoarthritic rats may be connected with the increased sensitivity of adenylate cyclase to the inhibitory effects of mu and delta agonists.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

PubMed1992

Endogenous opioid peptides in brain and pituitary of rats with absence epilepsy.

The level of opioid peptides in several brain areas and in the pituitary was estimated in WAG/Rij rats, which are considered to be a genetic animal model for human absence epilepsy. In comparison with three groups of non-epileptic controls, these epileptic rats had an elevated level of the proenkephalin-derived peptide Met-enkephalin-Arg6-Gly7-Leu8 in the mesencephalon and striatum, while the level of the prodynorphin-derived peptide alpha-neoendorphin was increased in the striatum and hippocampus. In addition various age- and/or strain-related changes in these peptide levels were found in the hippocampus, thalamus, striatum, frontal cortex and neurointermediate lobe of the pituitary. No difference in the hypothalamic beta-endorphin level were found between epileptic and non-epileptic rats, though strain- and/or age-related changes in the peptide content were detected in both lobes of the pituitary. The increased level of proenkephalin and prodynorphin opioid peptides in brain structures, essential for the appearance of spike-wave discharges, suggests that these opioid systems, but not proopiomelanocortin one, may play a role in absence epilepsy.

Animals↗

PubMed1992

The effects of excitatory amino acids on proenkephalin and prodynorphin mRNA levels in the hippocampal dentate gyrus of the rat; an in situ hybridization study.

Injection of N-methyl-D-aspartate (NMDA, 7.5 micrograms) kainate (1 microgram) or quisqualate (2 micrograms) into the rat dorsal hippocampus induced wet-dog shakes and convulsions. As shown by an in situ immunohistochemical analysis, 3 h after the excitatory amino acids injections the rats displayed a bilateral profound elevation of the proenkephalin and prodynorphin mRNA levels in dentate gyrus granule cells (2-3 or 1.5-2 fold higher than control levels, respectively). Pretreatment of rats with D-amino-phosphonovalerate (D-APV, 10 micrograms), a selective antagonist of NMDA receptor, prevented the behavioral and biochemical changes evoked by NMDA. The changes in the behavior and gene expression evoked by kainate or quisqualate were diminished in rats which received 6-cyano-7-nitroquinoxaline-2,3-dion (CNQX, 2 micrograms), a putative antagonist of quisqualate and kainate receptors. The study demonstrated that activation of NMDA, quisqualate or kainate receptors in the hippocampus induced seizures associated with a marked increase in the proenkephalin (PENK) and the prodynorphin (PDYN) gene expression in the rat dentate gyrus.

2-Amino-5-phosphonovalerate↗

PubMed1992

Time-dependent changes in the activity of opioid systems in the spinal cord of monoarthritic rats--a release and in situ hybridization study.

The activity of the endogenous opioid systems was analysed in the spinal cord of rats 12 h, one, five or 14 days after injection of the Freund Adjuvant into the hind limb sole. The tissue level of immunoreactive Met-enkephalin-Arg6-Gly7-Leu8, a peptide derived from proenkephalin, started to rise 12 h after Freund Adjuvant inoculation and remained enhanced until day 14. The spontaneous release of the immunoreactive Met-enkephalin-Arg6-Gly7-Leu8 was also elevated at all the examined time points, the peak occurring on day 1. No changes were observed in the stimulated release except on day 14, when the peptide release was decreased. The proenkephalin messenger RNA level was enhanced at all the time points on the ipsilateral side of the spinal cord in laminae I-II, whereas in lamina V an increase was observed only on days 1 and 5. An increase in the proenkephalin messenger RNA level on the contralateral side was observed only in laminae I-II and only on days 1 and 5. The tissue level of immunoreactive alpha-neoendorphin, a peptide derived from prodynorphin, was significantly increased on days 5 and 14. The spontaneous immunoreactive alpha-neoendorphin release from spinal cord slices was elevated at all the time points studied, whereas the stimulated release of the peptide was strongly increased 12 h after Freund Adjuvant inoculation but gradually declined on the following days. An in situ hybridization study showed that the prodynorphin messenger RNA level in laminae I-II was increased at all the examined time points.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

The prodynorphin system in the rat hippocampus is differentially influenced by kainic acid and pentetrazole.

Administration of kainic acid (15 mg/kg, i.p.) or pentetrazole (75 mg/kg, i.p.) to rats evoked recurrent limbic or tonic-clonic seizures, respectively. Radioimmunoassay showed that the level of alpha-neoendorphin (prodynorphin-derived peptide) in the hippocampus was decreased after 3 h (by c. 60%) and 72 h (by c. 40%), but was not changed after 24 h following kainic acid administration. The basal release of alpha-neoendorphin from hippocampal slices of kainic acid-treated rats was decreased after 3, 24 and 72 h following the drug injection by c. 50%. The K(+)-stimulated release was decreased after 3 and 24 h (by c. 300 and 200%, respectively) and was back to the control level after 72 h. An in situ hybridization study showed that kainic acid strongly enhanced the prodynorphin messenger RNA levels in the dentate gyrus after 3 and 24 h (by c. 200%), whereas after 72 h it tended to decrease. Twenty four hours after pentetrazole injection the hippocampal level of alpha-neoendorphin was elevated (by c. 33%) and remained unchanged after 3 and 72 h. No significant changes in the basal or K(+)-stimulated alpha-neoendorphin release from hippocampal slices of pentetrazole-treated rats were found at any time points measured. Three and 24 h after pentetrazole administration the level of prodynorphin mRNA in the dentate gyrus was slightly decreased (by c. 30%), but was back to the control values after 72 h. Hence seizure-related changes in hippocampal prodynorphin neuron activity seem to depend on the experimental model of epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗