Biomedical subjects

S Sagratella

Publications and source records attributed to S Sagratella.

At least 55 records · Page 3Linked to original sources

PubMed1993

Absence of calcium-induced LTP-like response in the dentate area of seizure-prone gerbils and its relation to parvalbumin in the entorhinal perforant path synapse of this species.

Mongolian gerbils (Meriones unguiculatus) are genetically predisposed to seizures, for which an involvement of hippocampal hyperexcitability and disinhibition has been suggested. The response in vitro of the hippocampal synaptic circuit upon exposure to an elevated extracellular calcium concentration is well known in the rat, and its dependence on inhibitory and excitatory transmission has been thoroughly studied. The purpose of the present investigation was to compare the influence of elevated extracellular calcium on inhibitory and excitatory transmission in the dentate area and the CA1 field of gerbil and rat hippocampal slices. Elevated calcium induced in the CA1 area of both animal species a long-term potentiation (LTP)-like response. Upon calcium exposure in the dentate area a decrease in population spike amplitude occurred in both gerbil and rat slices, indicating a similar degree of synaptic inhibition in the two species. However, in contrast to the effects known in the rat, elevated extracellular calcium failed to enhance the excitatory postsynaptic potential in the gerbil dentate area. This difference may depend on the species-specific, selective presence of the calcium-binding protein parvalbumin in perforant path terminals of the gerbil, which may be relevant to the susceptibility to seizures of this animal species.

Animals↗

PubMed1993

Effects of calcium and paired-pulse stimulation on hypoxia-induced hippocampal electrical changes.

The influence of calcium concentration changes (2 and 4 mM) and of the paired-pulse stimulation (PPS) paradigm on the effects of hypoxia has been investigated in rat hippocampal slices. Because a high calcium concentration (4 mM) facilitates paired-pulse inhibition (PPI) at a 15-ms interpulse interval, the influence of hypoxia-induced effects were tested against calcium-induced PPI. In the PPS, unconditioned response at calcium concentrations of 2 and 4 mM, and 15- or 30-ms interpulse intervals of stimulation, no significant differences were found in the latency to induce a 50% amplitude decrease of the CA1 population spikes during hypoxia. On the contrary, in the conditioned response the latency to induce a 50% amplitude decrease of CA1 population spikes was significantly increased (p < 0.01) at 4 mM calcium, 15-ms interpulse interval with respect to experiments with 2 mM calcium, at 15- or 30-ms interpulse intervals. The data indicate that PPI is strongly affected during the early phases of hypoxia and also suggest that drugs increasing PPI could be successfully used for the treatment of brief anoxic or ischemic functional alterations.

Animals↗

PubMed1993

In vivo and in vitro epileptogenic effects of the enkephalinergic system.

The relationships between the in vivo epileptogenic effects of opiates and the in vitro electrophysiological activity of opiates, enkephalins and inhibitors of endogenous peptidase were analyzed in order to ascertain the effective functional role of the endogenous opiate peptidergic system in the control of neuronal excitability. Morphine, enkephalins and related drugs induced in rats and rabbits naloxone-sensitive non-convulsive hippocampal EEG epileptiform activity after systemic or central administration. Higher doses of morphine and related drugs induced naloxone-insensitive convulsive EEG epileptiform activity within all the brain after systemic or central administration. Morphine and enkephalins, selectively acting at mu opiate receptors (DAGO, morphiceptin), increased in rat hippocampal slices the excitability of CA1 pyramidal cells, an effects revealed by a naloxone-sensitive increase of the magnitude of the CA1 population spike and by the appearance of several additional epileptiform population spikes. Enkephalins, selectively acting at delta opiate receptors (DPDPE, deltorphin), produced a naloxone-sensitive increase of the magnitude of the CA1 population spike but failed to induce the appearance of several additional epileptiform population spikes. Enkephalinase inhibitors (thiorphan, SCH32615) failed to affect the basal CA1 electrical response, but potential the epileptiform activity induced by DAGO. Collectively, the data indicate that hippocampal mu opiate receptors mediate the excitatory-epileptogenic effects of opiates.

Animals↗

PubMed1992

Different capability of N-methyl-D-aspartate antagonists to elicit EEG and behavioural phencyclidine-like effects in rats.

Phencyclidine (PCP), a drug inducing schizophrenia-like symptoms in humans, is reported to be a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) subtype of excitatory amino acid receptors. In rats, PCP produces three dose-dependent stages of EEG patterns: 1) increase of cortical desynchronization duration; 2) increase of the amplitude of the high-frequency (20-30 Hz) low-voltage (30-50 microV) cortical background activity; 3) appearance of cortical slow (2-3 Hz) wave-sharp wave complexes. These EEG changes are accompanied by stimulatory-depressive effects such as stereotypy (circling, head weaving) and ataxia. In the present study, the EEG and behavioural effects induced by systemic administration of the NMDA antagonists dizocilpine (MK 801), dextromethorphan (DM), [(+)-alpha-(4-chlorophenyl)-4- [(phenyl)methyl-1-piperidine ethanol] (SL 82.0715), (+)3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP), cis-4-phosphonomethyl-2-piperidine-carboxylic acid (CGS 19755) have been compared to those of PCP in rats. The rank of potency for inducing PCP-like EEG stages 1-3 was as follows: MK 801 > PCP > CGS 19755 > CPP. These drugs also induced PCP-like behavioural effects. On the contrary, DM and SL 82.0715, administered up to the dose of 100 mg/kg IP, failed to induce PCP-like behavioural effects and elicited only the stage 1 of PCP-like EEG. These results strongly suggest the involvement of NMDA neurotransmission in the behavioral and EEG effects of PCP.

Analysis of Variance↗

PubMed1992

Effects of adenosinergic drugs on hypoxia-induced electrophysiological changes in rat hippocampal slices.

The effects of adenosinergic antagonists caffeine and DPCPX, and of the adenosinergic agonists L-PIA, CPA and CGS 21680 were investigated on fully and partially reversible hypoxia-induced electrophysiological changes in rat hippocampal slices. The influence of a high potassium solution and of the N-methyl-D-aspartate antagonist dizocilpine (MK 801) was also tested. The latency to obtain a 50% decrease in the amplitude of the CA1 population spike (CA1 PS) during a short- (5-10 min) lasting hypoxic period was significantly increased (P less than 0.01) by slice perfusion with caffeine (50 microM), DPCPX (0.2 microM), and by increasing (from 3 to 4 mM) the potassium concentration in the medium bathing the hippocampal slices. The latency was significantly decreased (P less than 0.01) by slice perfusion with L-PIA (0.2 microM) and CPA (0.05 microM). It was not significantly modified by CGS 21680 (5 microM). The incidence of reappearance of the CA1 PS during reoxygenation after long- (45 min) lasting hypoxia was significantly increased (P less than 0.05) by slice perfusion with MK 801 (50 microM), while it was not significantly affected by slice perfusion with caffeine (50 microM) or DPCPX (0.2 microM) or L-PIA (0.2 microM) or CPA (0.05 microM) or CGS 21680 (5 microM). The results indicate a prevalent involvement of the A1 adenosine receptors in the early mechanisms underlying hypoxia-induced reversible changes. Adenosine seems to have a limited role in the late mechanisms occurring after a long-lasting hypoxic period.

Adenosine↗

PubMed1992

Inhibitory influence of morphinans on ictal and interictal EEG changes induced by cortical application of penicillin in rabbits: a comparative study with NMDA antagonists and pentobarbitone.

The effects of dextrorphan (DX) and dextromethorphan (DM) were tested using the electroencephalogram (EEG) and behavioral effects induced by topical cortical application of penicillin in rabbits. For comparison, the influence of the NMDA antagonists, dizocilpine (MK 801) and 3-((+-(-)2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP), and of pentobarbitone was investigated. Intracortical injection of 500 IU of penicillin produced an EEG spiking followed by a repeated generalization of the electrical and behavioral symptoms. Within a few minutes, DX (5-15 mg/kg, IV) or pentobarbitone (5-10 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the interictal and ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin. Higher doses of pentobarbitone (20 mg/kg, IV) but not of DX (20 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, MK 801 (0.1-0.2 mg/kg, IV) or CPP (10-20 mg/kg, IV) reduced dose dependently and significantly (p less than 0.01) the ictal EEG and behavioral effects elicited by cortical injection of 500 IU of penicillin, while they did not affect the penicillin-induced interictal EEG changes. Higher doses of MK 801 (0.3 mg/kg, IV) completely blocked the ictal behavioral and EEG effects elicited by cortical injection of 500 IU of penicillin. Within a few minutes, DM (10-20 mg/kg, IV) blocked the behavioral effects, but failed to affect either the interictal or the ictal EEG effects induced by cortical injection of 500 IU of penicillin.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Hippocampal long-term potentiation in nucleus basalis magnocellularis-lesioned rats.

The probability of hippocampal long-term potentiation induction in the mossy fiber CA3 and commissural/associational CA3 responses and the cortical levels of choline acetyltransferase (ChAT) activity were compared in right nucleus basalis magnocellularis (NBM)-lesioned rats. A 50% reduction in the right cortical ChAT activity was demonstrated 4 weeks after an ibotenic acid lesion of the NBM. No significative differences were found in the probability of LTP induction of right hippocampal slices in sham-operated rats from 10 to 40 days after the injection into the right NBM. On the contrary, a progressive and significative increase in the probability of LTP induction was shown in right hippocampal slices of NBM-lesioned rats from 10 to 40 days after the injection of ibotenic acid into the right NBM. The results demonstrated the appearance of a paradoxical increase of hippocampal synaptic plasticity when the cortical cholinergic biochemical alterations are still present. This finding might be responsible for a behavioural recovery, in NBM-lesioned rats.

2-Amino-5-phosphonovalerate↗

PubMed1992

Dexamethasone prevents epileptiform activity induced by morphine in in vivo and in vitro experiments.

The inhibitory effects exerted by dexamethasone on the epileptiform activity induced by morphine were investigated in two different experimental models with two different animal species. In the first series of experiments, dexamethasone administered i.v. in rabbits 30 min before i.c.v. administration of morphine completely prevented both epileptiform and background EEG as well as behavioral alterations induced by morphine. Cycloheximide (a protein synthesis inhibitor) pretreatment reversed the antagonistic effect induced by dexamethasone on the behavioral and EEG alterations induced by morphine. In the second series of experiments, the effects exerted by dexamethasone were investigated on morphine-induced CA1 epileptiform bursting on rat hippocampal slices in vitro. Dexamethasone pretreatment 10 to 60 min before morphine strongly prevented the morphine effects in a concentration- and time-dependent manner. Sixty min of dexamethasone pretreatment also prevented the epileptiform bursting induced by the selective mu opiate receptor agonist DAMGO, whereas it did not significantly affect the increase of the CA1 population spike amplitude due to the selective delta opiate receptor agonist DPDPE. The addition of cycloheximide to the slice-perfusing medium containing dexamethasone prevented the inhibitory effects of the drug toward the morphine and DAMGO-induced CA1 epileptiform bursting. Our results indicate that dexamethasone induces an inhibition on the epileptiform activity induced by morphine and DAMGO. The time lag (30-60 min) which is necessary for revealing the inhibitory influence of dexamethasone on opiate epileptiform activity induced both in vivo and in vitro, and the inhibitory effect exerted by cycloheximide on dexamethasone activity strongly support the hypothesis of a genomic corticosteroid effect within the central nervous system.

Animals↗

PubMed1991

Behavioural and electoencephalographic interactions between haloperidol and PCP/sigma ligands in the rat.

Phencyclidine (PCP) and sigma ligands produce a typical excitatory behaviour in rats, characterized by circling and head- and body-weaving. Excitatory amino acid antagonists such as 2-amino 5-phosphonovaleric acid (AP5) or 3-(+/-)-2-carboxypiperazin-4-yl)propyl-l-phosphonic acid (CPP) also produce a PCP-like excitatory behaviour in rats. In the present paper, the interactions between PCP/sigma drugs or excitatory amino acid receptor antagonists and haloperidol have been investigated in rats. In addition, the influence of two other butyrophenones having a different affinity for the sigma/haloperidol receptors, such as spiperone and 3-(4-(3(4-fluorobenzoyl)-propyl-piperazino-l-yl-isoquinolino (HR 375), has been tested on the behavioural and EEG effects of PCP/sigma drugs and excitatory amino acid antagonists. PCP (2.5-5 mg/kg IP), (+) or (-) SKF 10,047 (1-15 mg/kg IP), (+) or (-) cyclazocine (2-8 mg/kg IP) and AP5 (0.5 mumol ICV) dose-dependently and significantly (P less than 0.01) antagonized the haloperidol-induced catalepsy in the horizontal bar and podium tests in rats. On the other hand, either haloperidol (1 mg/kg IP) or spiperone (1 mg/kg IP) reduced the head-weaving induced by (+) SKF 10,047, PCP, or AP5. On the contrary, HR 375 (6 mg/kg IP) was ineffective in blocking the excitatory effects of these drugs. In addition, either haloperidol (1 mg/kg IP) or spiperone (1 mg/kg IP), but not HR 375 (6 mg/kg IP) reduced the amplitude increase of the fast (20-30 Hz) frequency/low (30-50 microV) voltage background cortical activity elicited by PCP or (+) SKF 10,047. The results demonstrate an interaction between dopamine and excitatory amino acid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗

PubMed1991

Aminoglycoside antibiotics affect hippocampal LTP: a comparative study with the N-type calcium antagonist omega-conotoxin-GVIA.

The in vitro activity of N-type calcium antagonists such as omega-conotoxin-GVIA and the aminoglycoside antibiotics neomycin and streptomycin was studied in rat hippocampal slices. The effects of the drugs were tested on basal CA1 synaptic transmission and on the hippocampal long-term potentiation (LTP) induced by tetanic electrical stimulation and by increasing (4mM) the calcium concentration. Omega-conotoxin-GVIA, neomycin and streptomycin were able to significantly reduce the amplitude of the CA1 population spike at 1 microM, 0.5 mM and 1 mM, respectively. In addition, the drugs affected the induction and maintenance of the CA1 tetanic and calcium-induced LTP at concentrations which did not modify the magnitude of the control CA1 population spike. Omega-conotoxin-GVIA (0.5 microM), neomycin (0.3 mM) and streptomycin (0.7 mM) perfused for 60 min, before inducing LTP, prevented the subsequent increase of the CA1 population spike in all the experiments. The same concentrations of these drugs perfused for 60-min after a previously established LTP significantly reduced the amplitude of the CA1 population spike. The results promote a role for the N-type calcium channels and for the release of neurotransmitters in both the induction and the maintenance of hippocampal LTP.

Action Potentials↗

PubMed1991

In vitro depressant effects of U-54494A, an anticonvulsant related to kappa opioids, in the hippocampus.

The effects of cis-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl-benzamide (U-54494A), an anticonvulsant related to kappa opioids, were studied in vitro on the extracellular electrical activity of the CA1 region of slices of hippocampus in the rat. The effects of U-54494A were compared to those of the kappa opioid agonist trans-3,4 dichloro-N-2-(1-pyrrolidinyl)cyclo-hexyl benzeneacetamide methane sulphonate (U-50488H). Both U-54494A and U-50488H, in concentrations of 50 and 100 microM, respectively, reduced the magnitude of the orthodromically evoked CA1 population spikes after electrical stimulation of the stratum radiatum (100-200 microA, 70 microseconds, 0.1 Hz). Naltrexone (25 microM), or the selective kappa opiate receptor antagonist, 1-cyclopenthyl-5-(1,2,3,4,5,6-hexahydroxy-3,6,11-trimethyl-2 -6-methano-3- benzazocin)-3-pentatone methane sulphonate (WIN 44441-3) (25 microM), prevented the depressant activity of U-54494A (200 microM) on the CA1 population spikes. High calcium (+3mM) solutions prevented the depressant activity of increasing concentrations of both U-54494A and U-50488H on the amplitude of CA1 population spikes. Up to 200 microM, both drugs were ineffective in depressing the epileptiform bursting in CA1, due to 1 mM penicillin or to perfusion of the slice in absence of magnesium ions. The results demonstrate: (1) the inability of U-54494A to show antagonistic activity in two in vitro models of interictal epilepsy; (2) a depressant effect of U-54494A on basal synaptic transmission in the CA1 region of the hippocampus, which may be related to an influence on transneuronal calcium currents and which may be involved in the reported antagonism of ictal epileptic seizures by drugs.

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

PubMed1991

An in vitro study on the hippocampal electrophysiological properties of enkephalinase inhibitors in rats.

The effects of two enkephalinase inhibitors were studied on the CA1 and dentate hippocampal extracellular field potentials (FPs). The enkephalinase inhibitors thiorphan and SCH 32615, at a concentration of 1-500 microM, failed to significantly affect CA1 and dentate FPs. Thiorphan and SCH 32615, at a concentration of 150 microM, were able to potentiate the enkephalin-induced epileptiform bursting, inducing an increase in the bursting duration and in the number of spikes per burst due to 3.5 microM DAEAM or 0.20 microM DAGO. The results suggest: 1) the potentiation of an electrophysiological opiate receptor-mediated response by enkephalinase inhibitors; 2) the inability to show a direct effect on the basal CA1FP as a result of the inhibition of the endogenous enkephalinase.

Animals↗

PubMed1991

An in vitro study on the hippocampal epileptogenic properties of enkephalins and enkephalinase inhibitors in rats.

1. The effects of enkephalins and enkephalinase inhibitors were studied in CA1 area in rat hippocampal slices. 2. The data demonstrate a prevalent involvement of mu opiate receptors in the epileptogenic properties of enkephalins. 3. A potentiation of the mu opiate receptor-mediated epileptogenic response by enkephalinase inhibitors has been shown. 4. The results also show an inability to affect basal CA1 field potentials by inhibition of endogenous endopeptidase.

Animals↗

PubMed1991

Effects of some calcium antagonists and of calcium concentration changes on CA1 paired pulse inhibition in rat hippocampal slices.

1. In rat hippocampal slices, the lowering of the calcium concentration (from 2 to 1 mM) or diltiazem (200 microM) or CdCl2 (50 microM) significantly (P less than 0.01) increased the amplitude and shifted the stimulus-response curve of the secondary population spikes, due to paired pulse CA1 stimulation to the left. 2. The amplitude of the primary population spikes was not significantly affected. 3. The data demonstrated that the role of the concentration of calcium ions is critical in control of local inhibitory hippocampal circuitry at the base of paired pulse inhibition.

Animals↗

PubMed1991

Diversified electrophysiological properties of morphinan drugs in rats.

1. In in vivo and in vitro studies in rats, the effects of dextromethorphan (DM), dextrorphan (DX), and levorphanol (LV) were compared with those induced by kappa and sigma opiate agonists. 2. In rat hippocampal slices all the morphinans were able to pertubate the CAI hippocampal synaptic transmission, while only DX and LV affected the N-methyl-D-aspartate excitability through a possible interaction at sigma opiate receptors. 3. On the other hand EEG studies show that only DX appears to act as a full agonist at sigma opiate receptors. 4. Present data demonstrate diversified electrophysiological properties of morphinans both in in vitro and in vivo studies.

Animals↗

PubMed1991

Effects of calcium and potassium extracellular ionic concentration changes on the hippocampal CA1 activity of purinergic drugs.

1. The influence of the change of potassium and calcium concentrations in the medium bathing hippocampal slices has been tested on the purinergic drug effects. 2. The depressive effect of purinergic agonists were antagonized by 50% by doubling the potassium concentration, while they were not affected by doubling calcium concentrations. 3. The data demonstrate a direct intrinsic activity of potassium ions, and suggest a possible direct interaction between adenosine receptors and potassium transneuronal fluxes.

4-Aminopyridine↗

PubMed1991

Cromakalim (BRL 34915) counteracts the epileptiform activity elicited by diltiazem and verapamil in rats.

1. The effects of BRL 34915 (cromakalim), a potassium channel opener, have been tested on the epileptiform activity elicited by high dose/concentrations of some calcium antagonists in in vivo (diltiazem) and in vitro (diltiazem and verapamil) experiments in rats. 2. Diltiazem (150-300 mg kg-1, i.p.) induced behavioural and electroencephalographic (EEG) seizures that were completely prevented by cromakalim (10 nmol/10 microliters, i.c.v.). Whereas, pentobarbitone (5-10 mg kg-1, i.p.) only prevented the behavioural component of the seizures. 3. In hippocampal slices, verapamil (1.5-2.0 mM) produced, within 30-60 min of perfusion, a CA1 epileptiform bursting in 80% of the experiments. This epileptiform activity was prevented by the cromakalim concentration (50 microM) that did not affect the control CA1 synaptic transmission per se. Pentobarbitone also prevented verapamil-induced epileptiform bursting only at the concentration (100 microM) that also reduced control CA1 synaptic transmission. 4. Diltiazem (1.5 mM) produced a biphasic excitatory-depressant effect within 60 min of perfusion. A CA1 epileptiform bursting appeared in 100% of the experiments within 30 min of perfusion. These excitatory effects were followed by a depression phase, characterized by a reduction of the magnitude of CA1 excitatory postsynaptic potentials (e.p.s.ps) and population spike. 5. The diltiazem-induced epileptiform bursting was prevented by cromakalim at a concentration (50 microM) that did not affect the control CA1 synaptic transmission per se. Pentobarbitone also prevented the diltiazem-induced epileptiform bursting only at a concentration (100 microM) that also reduced the control CA1 synaptic transmission. Both cromakalim (50 microM) and pentobarbitone (100 microM) failed to affect the depressant effects of diltiazem on CA1 hippocampal area. On the contrary, high (3.3mM) calcium solutions prevented both the excitatory and the depressant effects of 1.5 mm diltiazem within 60 min.6. These data indicate an involvement of potassium currents in the epileptiform activity elicited by high doses of diltiazem and verapamil.

Animals↗

PubMed1990

Inhibitory influence of excitatory amino acid antagonists on penicillin-induced epileptiform bursting in rat hippocampal slices.

The inhibitory influence of excitatory amino acid (E.A.A.) antagonists such as kynurenic acid, 2-amino-5-phosphonopentanoic acid (AP5), cis-2,3-piperidine dicarboxylic acid (cis-2,3 PDA) and (+)-5-methyl-10,11,-dihydro-5H-dibenzo(a,d)cyclo-hepten-5,10-imine maleate (MK 801), has been studied on the epileptiform activity elicited in rat hippocampal slices, bathed in penicillin (1 mM). The rank of the inhibitory potency was: MK 801 greater than kynurenic acid greater than cis 2,3 PDA greater than AP5. Moreover, only MK 801 was able to block the last population spike of the penicillin-induced epileptiform bursting in 100% of the experiments. The data indicate that the antiepileptic activity of E.A.A. antagonists on the penicillin epileptiform bursting in CA1 pyramidal cells is low and limited, indicating that the hippocampal area is not the primary site of the anticonvulsant activity of E.A.A. antagonists.

Amino Acids↗