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S Sagratella

Publications and source records attributed to S Sagratella.

At least 73 records · Page 4Linked to original sources
PubMed1990

High calcium solutions prevent the depressant effects of aminoglycoside antibiotics on central synaptic transmission in rat hippocampal slices.

1. The aminoglycoside antibiotics neomycin and streptomycin were tested on the synaptic activity of the CA1 pyramidal neuron-Schaffer collateral interconnections in rat hippocampal slices. 2. Neomycin (0.5 mM) decreased the magnitude and shifted to the right the stimulus-response curve of the somatic and dendritic excitatory postsynaptic potential (EPSP) and the somatic population spike (PS). 3. Streptomycin (1 mM) decreased the magnitude and shifted to the right the stimulus-response curve of the somatic and dendritic EPSP and the somatic PS. 4. High (+2 mM) calcium solutions were able to prevent the effects induced by the antibiotics and to shift to the left the stimulus-response curve of the 0.5 mM neomycin and 1 mM streptomycin treated hippocampal slices. 5. The data demonstrate an effect of aminoglycoside antibiotics on a central mammalian hippocampal synapses, that may depend on an interference of the drugs on calcium conductances.

Animals↗
PubMed1989

Behavioural and electroencephalographic effects of excitatory amino acid antagonists and sigma opiate/phencyclidine-like compounds in rats.

The present work was a comparative study of the electrocortical and behavioural effects of phencyclidine-like drugs and sigma-opiate drugs and of some excitatory amino acid antagonists. Phencyclidine-like drugs and sigma-opiate drugs elicited three dose-dependent electrocortical patterns: 1. Increase of periods of cortical desynchronization 2. Increase of the amplitude of fast (20-30 Hz) cortical waves; 3. Appearance of typical cortical complexes consisting of slow-wave (0.5-2 Hz) sharp-wave complexes. These effects were accompanied by excitatory motor symptoms, such as stereotyped movements of the neck and limbs. The NMDA competitive antagonist D,L-2-amino-5-phosphonovaleric acid (D,L-AP5), administered intracerebroventricularly (0.25-2 mumol), elicited phencyclidine-like stereotyped behaviour and cortical desynchronization, but failed to elicit/sigma typical cortical complexes. The non-selective amino acid antagonist cis-2,3 piperidine dicarboxilic acid (cis 2,3-PDA), administered intraperitoneally (3.3 mmol) failed to elicit both stereotyped behaviour and typical phencyclidine/sigma cortical complexes. The results strongly suggest the hypothesis that a reduction of excitatory amino acid neurotransmission, utilizing N-methyl-d-aspartate (NMDA)-preferring receptors, may be involved in the genesis of phencyclidine/sigma-induced stereotyped behaviour.

2-Amino-5-phosphonovalerate↗
PubMed1989

An electrophysiological study on the common antitussive drug dextromethorphan in hippocampal slices in the rat.

Dextromethorphan, a common antitussive drug derived from the opioid class of morphinans, has been reported to have antiepileptic properties in some experimental tests. The effects of dextromethorphan were tested on the synaptic responses of the interconnections between Schaffer collaterals and CA1 pyramidal cells in hippocampal slices of the rat. Dextromethorphan, up to 100-200 microM, did not affect the basal field potentials resulting from electrical stimulation of the radiatum (0.1 Hz, 100-200 microA, 75 mu sec) of CA1 pyramidal cells. Larger concentrations of the drug (300-400 microM) depressed the amplitude and increased the duration of the CA1 basal population spikes. Dextromethorphan, up to 200-300 microM, affected neither the duration nor the incidence of the additional population spikes of the epileptiform bursting, resulting from perfusion of the slice with 1 mM penicillin or in the absence of magnesium ions. The data indicate that: (1) dextromethorphan has an influence on CA1 pyramidal cells, different from that of other opioids; (2) the reported antiepileptic effects of dextromethorphan do not involve the hippocampal area.

Animals↗
PubMed1989

Pharmacology of calcium-induced long-term potentiation in rat hippocampal slices.

A transient increase (10 min) in extracellular calcium concentration (4 mM) causes a long-lasting (greater than 2 hr) enhancement of population spike responses evoked by radiatum fibers to CA1 pyramidal neurons in rat hippocampal slices. This phenomenon is similar to tetanic long-term potentiation (LTP), and is also related to memory processes. The influence of various drugs was investigated on calcium-induced LTP. The NMDA antagonist 2 amino-5-phosphonopentanoic acid (AP5; 100 microM) was able to prevent the calcium-induced LTP, while atropine sulphate (10 microM), propranolol hydrochloride (10 microM) and verapamil hydrochloride (100 microM) were ineffective. The results suggest an involvement of the NMDA receptor in the development of calcium-induced LTP.

2-Amino-5-phosphonovalerate↗
PubMed1989

Pentobarbital-like electroencephalographic rubral rhythm induced by ketamine in rabbits.

1. The effects caused by the dissociative anaesthetic drugs (PCP, KT), the sigmaopiates (SKF 10.047, cyclazocine), and the mixed excitatory amino acid antagonist CCP on the electrical activity of the red nucleus in rabbits were compared with PB. 2. Ketamine (10 mg/kg, i.v.) induced the appearance of a pentobarbital-like EEG synusoidal rhythm characterized by an increase in amplitude and a decrease in frequency of the basal electrical activity at the red nucleus level. 3. Both pentobarbital and ketamine induced rhythms were blocked by the GABA-antagonist pentylenetetrazol at the subconvulsant dose of 10 mg/kg, i.v. 4. Phencyclidine, SKF 10.047, cyclazocine, and the mixed excitatory amino acid antagonist CCP failed to affect the basal electrical activity of the red nucleus. 5. These data indicate an interaction of ketamine on the GABA neurotransmission at the level of cerebello-rubral pathways which the other PCP/sigma opiates did not present.

Animals↗
PubMed1988

Comparative influence of calcium blocker and purinergic drugs on epileptiform bursting in rat hippocampal slices.

Caffeine (50 microM) increases the amplitude of the basal field potential (BFP) due to orthodromic stimulation of CA1 pyramidal neurons in rat hippocampal slices. This effect is absent if (1) the adenosine agonist L-phenyl-isopropyladenosine (L-PIA) (0.5 microM) is added to the perfusion with caffeine, and (2) low calcium (0.1 mM)-high magnesium (5mM) solutions are used. The calcium blocker verapamil (0.05-0.2 mM) does not modify the caffeine-induced effects. Higher concentrations of caffeine (0.2-0.5 mM) elicit the appearance of an epileptiform bursting, whose duration is inhibited at almost the 50% by 0.5 microM of L-PIA and unaffected by verapamil (0.2 mM) and nifedipine (0.05-0.10 mM). 5 microM of L-PIA, low calcium (0.1 mM)-high magnesium (5 mM) solution and verapamil (0.2 mM) are able to inhibit at almost the 50% the epileptiform bursting duration due to the potassium blocker 4-aminopyridine (4-AP). Nifedipine (0.05-0.1 mM) does not affect the 4-AP effects. L-PIA (0.5-2 microM) but not verapamil (0.2 mM) and nifedipine (0.1 mM) inhibits at almost the 50% the penicillin (1 mM) epileptiform bursting duration. The data indicate a different antagonistic influence of purinergic drugs and verapamil, on different models of epilepsy in rat hippocampal slices. In addition, the lack of antagonism between purinergic drugs and verapamil suggests different sites of action of the drugs.

Adenosine↗
PubMed1987

Effects of ketamine and (+)cyclazocine on 4-aminopyridine and "magnesium free" epileptogenic activity in hippocampal slices of rats.

The effects of ketamine and (+)cyclazocine on three in vitro models of epilepsy: the "Mg2+ free", the 4-aminopyridine (4-AP) and, for comparison, the penicillin model were studied. These data indicate that the two compounds had an inhibitory effect in hippocampal slices of rats, bathed in "Mg2+ free" solution at a concentration that did not influence the basal field potential. They also had an inhibitory effect on the penicillin model, but at concentrations ten times greater than those effective against "Mg2+ free" model. On the other hand, (+)cyclazocine was equally active against epileptogenic activity produced by 4-AP and "Mg2+ free" solution, while ketamine failed to produce an effect on epileptiform activity induced by 4-AP.

2-Amino-5-phosphonovalerate↗
PubMed1987

Modulatory action of purinergic drugs on high potassium-induced epileptiform bursting in rat hippocampal slices.

Increase of the potassium concentration up to 8 mM in the superfused solution of rat hippocampal slices leads to the development of an epileptiform bursting. The derivative agonist L-phenyl isopropyl adenosine (L-PIA) (0.05-0.5 microM) is able to block the potassium induced epileptiform activity. The adenosine antagonist caffeine (100 microM) reverts the antiepileptic effect of L-PIA. Our data show a modulatory action of the purinergic transmission in a model of experimental in vitro epilepsy, and point out about a control of endogenous adenosine in the development of focal epileptiform activity. The relationships between the purinergic influence on the release of neurotransmitters, and the convulsant-anticonvulsant effects of the drugs are discussed.

Animals↗
PubMed1987

SCH 23390 and its S-enantiomer stereoselectively prevent EEG and behavioral activation induced by dopamine agonists in the rabbit.

The selective D-1 dopamine antagonist SCH 23390 (R-enantiomer) and its unselective S-enantiomer (SCH 23388) were compared for their ability to prevent EEG and behavioral activation induced by the dopamine receptor agonists SKF 38393, apomorphine and LY 171555 in the rabbit. SCH 23390, at very low doses (0.003 mg/kg IV), inhibited EEG responses elicited by SKF 38393 and apomorphine, while the S-enantiomer displayed similar effects at doses at least 300-fold higher (1-3 mg/kg IV). Both isomers were approximately equipotent in preventing behavioral excitation caused by the D-2 agonist LY 171555. The dose of SCH 23390 interacting with LY 171555 was at least 100-fold higher than that effective for D-1 mediated responses. Conversely, the doses of S-enantiomer which prevented the stimulating effects induced by the different dopamine agonists were similar. The data demonstrate the stereoselectivity of the R-isomer SCH 23390 for blockade of D-1 receptors in vivo and provide evidence for the sensitivity of the EEG models in studying D-1 mediated responses.

Animals↗
PubMed1987

An EEG and behavioural study on the excitatory properties of caffeine in rabbits.

In the present work we have investigated some of the excitatory effects of caffeine in rabbits. Caffeine (5-50 mg/kg i.v.) elicited a cortical EEG desynchronization and an activation of the theta hippocampal rhythm but failed to affect the red nucleus activity. The EEG effects of caffeine were counteracted by L-PIA (1-3 mg/kg i.v.). Caffeine (25-50 mg/kg i.v.) completely reverted the EEG and motor effects due to L-PIA (1-5 mg/kg); the drug also counteracted the cortical and hippocampal EEG modifications elicited by diazepam (1-10 mg/kg), but failed to influence the diazepam-induced effects at the red nucleus level. In addition, caffeine (25 mg/kg) significantly increased the duration of the epileptiform EEG response (afterdischarge) elicited by electrical stimulation of the dorsal hippocampus. This caffeine-potentiating effect was reduced by administration of both L-PIA (0.05-2 mg/kg) and diazepam (1 mg/kg); Ro 15-1788 (1 mg/kg) was unable to affect it. Present data suggest that the analeptic action of caffeine is different from that of the drugs acting through the GABA-benzodiazepine system. Our results show the importance of the limbic system in the excitatory effects of caffeine and suggest that purinergic drugs may have a modulatory role in the control of limbic convulsions.

Animals↗
PubMed1986

An EEG investigation on nabilone, a synthetic cannabinoid, in rabbits.

In this paper, the electroencephalographic (EEG) and behavioural effects of nabilone, a derivative compound from delta 9-tetrahydrocannabinol (delta 9-THC), are studied in comparison with those of delta 8-tetrahydrocannabinol (delta 8-THC) in rabbits. The results show that nabilone requires lower doses than delta 8-THC to elicit cortical spike-and-wave complexes, but higher doses to disrupt hippocampal theta rhythm. These data are discussed in connection with the clinical actions of nabilone in man.

Animals↗
PubMed1985

An investigation on the mechanism of anticonvulsant action of ketamine and phencyclidine on convulsions due to cortical application of penicillin in rabbits.

The intracortical injection of 500 units of penicillin in rabbits elicited intermittent bilateral spikes or spike-wave complexes followed by generalization of the epileptiform activity characterized by repeated ictal high-voltage, high frequency spikes paralleled by generalized convulsions. Administration of phencyclidine (PCP) (0.7-1.0 mg/Kg i.v.), ketamine (KT) (20-40 mg/Kg i.v.), pentobarbital (PB) (10 mg/Kg i.v.) and diazepam (3 mg/Kg i.v.) inhibited the generalization of the epileptiform activity induced by penicillin (500 units) counteracting the EEG and motor patterns of the ictal events, while did not influence the interictal spike-and-wave complexes. Physostigmine (0.1 mg/Kg i.v.), clonidine (0.1 mg/Kg i.v.), haloperidol (1 mg/Kg i.v.) and naloxone (10 mg/Kg i.v.) did not affect the inhibitory influence of PCP on epileptiform activity due to cortical application of penicillin. Thus, the mechanism of this anticonvulsant action of PCP seems not to depend on the neurotransmitter system related to the reported drugs. The mechanism of action of PCP and KT is discussed in connexion with the similarities of the effects of this drugs in respect to sigma opiate agonists and pentobarbital.

Animals↗
PubMed1985

Phencyclidine-like effect of cyclazocine on pentylentetrazol-induced seizures in laboratory animals.

The present work deals with an EEG and behavioural study of the effect of cyclazocine against the convulsions due to pentylentetrazol (PTZ) in mice, rats and rabbits. In rats, cyclazocine, at the high doses (15-25 mg/kg) prevents the tonic motor convulsions and EEG epileptiform "grand mal" seizure induced by PTZ. In rabbits and mice, cyclazocine inhibits the tonic motor convulsions without modifying either the spike-frequency or the duration of the PTZ-induced EEG seizures. Naloxone, even at high doses, was not able to block the anticonvulsive effects of cyclazocine on PTZ-induced convulsions in the rat. The effects of cyclazocine were compared to those of phencyclidine. These results confirm the multiple behavioural effects of cyclazocine and support the idea that both cyclazocine and phencyclidine, may act on the PCP/sigma receptor identified in binding studies.

Animals↗
PubMed1985

An EEG investigation on the role of cerebello-rubral system in the effects of diazepam and pentobarbital.

The EEG effects of diazepam and pentobarbital at the level of cerebello-rubral pathways (i.e., cerebellar cortex, interposed, fastigial and red nuclei) were studied. The drugs elicited a slowing of frequency and an enhancement of the voltage of the waves at the level of cerebellar and red nucleus leads. The effect was antagonized by picrotoxin or pentamethylenetetrazole, while ethyl - 8 - fluoro - 5,6 - dihydro - methyl-6-oxo-4H-imidazol [1,5 a][1,4]benzodiazepin-3-carboxylate (Ro 15-1788) antagonized only the effect of diazepam. The relationships between the EEG alterations and the behavioural effects of diazepam and pentobarbital, which are endowed with muscle relaxing, sedative-anesthetic and anticonvulsant activity, are discussed.

Animals↗
PubMed1984

Chronic administration of diazepam to rats causes changes in EEG patterns and in coupling between GABA receptors and benzodiazepine binding sites in vitro.

The daily administration of diazepam (10 mg/kg i.v.) in rats elicited tolerance to the sedative effect within 2-3 days, parallel to the emerging of a stimulatory syndrome. In the EEG, the latter was accompanied by a progressive replacement of the trains of spindles with 25-30 Hz low amplitude waves. No clear signs of tolerance to the myorelaxant effect of diazepam were observed. After 10 days of treatment, the drug was discontinued. Thereafter, a single administration of diazepam elicited a stimulatory syndrome and EEG desynchronization throughout the 15 days of withdrawal. [3H]diazepam binding studies, performed in frozen-thawed membrane preparations incubated at 37 degrees C for 30 min, showed a decrease of KD values in tolerant rats up to 7 days after discontinuation of the drug. In parallel, a reduction in the ability of GABA to enhance [3H]diazepam binding, as well as to protect [3H]diazepam recognition sites from thermoinactivation at 60 degrees C, were found in tolerant rats up to 15 days after drug termination. These data suggest that a modification in the regulatory activity of GABA on benzodiazepine recognition sites might underlie the tolerance to the sedative effects and EEG changes of benzodiazepines.

Animals↗