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A Siniscalchi

Publications and source records attributed to A Siniscalchi.

16 recordsLinked to original sources
PubMed1992

Modulation by GABAB receptors of spontaneous synchronous activities induced by 4-aminopyridine in the rat hippocampus.

Field potential recordings were made in the CA3 and/or CA1 subfields of rat hippocampal slices maintained in vitro during perfusion with medium containing the convulsant drug 4-aminopyridine (4AP, 50 microM). In this experimental condition, spontaneous interictal epileptiform discharges caused by the activation of excitatory amino acid receptors and synchronous, GABA-mediated potentials occurred regularly in both areas. Interictal discharges and GABA-mediated potentials were reduced and eventually abolished in both subfields by bath application of baclofen (0.5-100 microM), which is a selective agonist for the GABAB receptor. However, interictal epileptiform events disappeared in the presence of baclofen concentrations (i.e., 4.75 +/- 0.7 microM; IC50 = 3.4 microM; n = 9) that were lower than those required for abolishing the GABA-mediated potential (i.e., 96.1 +/- 19.4 microM; IC50 = 9.8 microM; n = 12). The effects of baclofen were antagonized by the GABAB receptor antagonists saclofen (1 mM; n = 3 slices) or CGP 35348 (0.2-1 mM; IC50 = 240 microM; n = 12 slices). Our findings indicate that activation of GABAB receptors by baclofen inhibits both types of 4AP-induced activities in the rat hippocampus although epileptiform discharges appear to be more sensitive than GABA-mediated potentials to this pharmacological procedure. Although our data do not indicate whether the action of baclofen is pre- or postsynaptic, they demonstrate that this mechanism is sensitive to available GABAB receptor antagonists.

4-Aminopyridine↗
PubMed1992

Muscarinic modulation of acetylcholine release from slices of guinea pig nucleus basalis magnocellularis.

Spontaneous and electrically evoked endogenous acetylcholine release and [3H]-choline efflux from slices of guinea pig nucleus basalis magnocellularis (nbM) were studied. Tetrodotoxin reduced the spontaneous endogenous release by 55%, while the Ca(2+)-free medium reduced it by about 30%. Evoked [3H]-choline efflux was Na+ and Ca2+ dependent and frequency related. Physostigmine, 30 microM, nearly halved the stimulation-evoked efflux; atropine, 0.15 microM, not only antagonized, but even reversed this effect into facilitation. Pirenzepine, 1 microM, and AFDX 116, 1 microM, were less effective than atropine, and reversed the inhibitory effect of physostigmine only when applied together. 4-DAMP, 0.01 microM, was ineffective. These findings indicate that acetylcholine release in guinea pig nbM slices is inhibited by the cooperation of muscarinic autoreceptors, possibly belonging to the M1 and M2 subclasses.

Acetylcholine↗
PubMed1991

Influence of acute and chronic chlorimipramine treatment on the 5-HT receptor-mediated modulation of acetylcholine release from the cerebral cortex of freely moving guinea-pigs.

1. Acetylcholine (ACh) release from the cerebral cortex of freely moving guinea-pigs, implanted with epidural cups, was studied. 2. A single dose of chlorimipramine (Cl-Imip, 10 mg kg-1, s.c.), reduced the cortical ACh release both in normal and in chronically (10 mg kg-1 daily, s.c., for 14 days) Cl-Imip-treated guinea-pigs; the 5-HT3 antagonist MDL 72222 (1 mg kg-1, s.c.) antagonized this effect. 3. A single dose of Cl-Imip significantly reduced the effect of the 5-HT1A agonist 8-hydroxy-2-(di-n-propylaminotetralin) (8-OH-DPAT, 0.1 mg kg-1, s.c.), which nearly doubled the cortical ACh release in control animals. MDL 72222 restored to normal the response to 8-OH-DPAT reduced by the anti-depressant. 4. A single dose of Cl-Imip did not change the inhibitory, MDL 72222-sensitive, effect induced by the 5-HT3 agonist 2-methyl-5-hydroxytryptamine (2-methyl-5-HT, 500 micrograms, i.c.v.). 5. In chronically Cl-Imip-treated guinea-pigs, the facilitatory effect of 8-OH-DPAT was no longer present, while the inhibitory, MDL 72222-sensitive, effect of 2-methyl-5-HT was maintained. 6. These results indicate that the 5-HT1A receptor-mediated increase in ACh release is reduced by prolonged Cl-Imip treatment, while the 5-HT3 receptor-mediated inhibition of ACh release is unaffected. The relevance of these findings to the antidepressant mechanism of Cl-Imip is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Different effects of 8-OH-DPAT, a 5-HT1A receptor agonist, on cortical acetylcholine release, electrocortigram and body temperature in guinea pigs and rats.

8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) dose dependently increased cortical acetylcholine (ACh) release and the body temperature of freely moving guinea pigs. Moreover, it evoked an electroencephalographic (EEG) arousal reaction in phenobarbital-pretreated animals. 8-OH-DPAT was about 10 times less effective in increasing cortical ACh release in the rat than in the guinea pig, and did not modify the phenobarbital-synchronized EEG but dose dependently decreased body temperature. The possibility that 5-HT1A receptors play different roles, depending on the animal species, is discussed.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1990

Influence of chronic chlorimipramine treatment on the serotonergic modulation of acetylcholine release from guinea pig caudate nucleus slices.

The influence of chronic chlorimipramine (10 mg/kg daily s.c. for 14 days) treatment (CCT) on 5-HT modulation of basal 3H-choline overflow from guinea pig caudate nucleus slices was studied. The increase in basal tritium overflow induced by 5-HT (3-100 mumol/l) or by DOI (30-100 mumol/l) in normal slices was significantly lower in CCT slices. When tetrodotoxin 0.5 mumol/l was added, the facilitatory effect by 5-HT was cancelled, its late inhibitory effect became more evident and to the same extent in normal and CCT slices. This inhibition was cancelled by ICS 205-930 30 mumol/l. These results indicate that the 5-HT2-mediated facilitatory response of intrastriatal cholinergic neurones to 5-HT is reduced by CCT, while the inhibitory response is unaffected.

Acetylcholine↗
PubMed1990

5-HT1A agonists increase and 5-HT3 agonists decrease acetylcholine efflux from the cerebral cortex of freely-moving guinea-pigs.

1. The influence of 5-hydroxytryptamine1A (5-HT1A), 5-HT2 and 5-HT3 agonists and antagonists on acetylcholine (ACh) release from the cerebral cortex was studied in freely moving guinea-pigs. 2. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-1 mg kg-1, s.c.) caused the 5-HT syndrome and dose-dependently increased ACh release. Ru 24969 (1-10 mg kg-1, s.c.) shared the same effects, but it was less potent. (-)-Propranolol (5 mg kg-1) and metitepine (2 mg kg-1) prevented these behavioural and neurochemical responses. 3. (+/-)-1(4-Iodo-2,5-dimethoxyphenyl)2-aminopropane (DOI) up to 2 mg kg-1 did not modify ACh release and ketanserin (0.5 mg kg-1) was ineffective on 5-HT-induced changes of ACh outflow. 4. 2-Methyl-5-HT (500 micrograms, i.c.v.) and 5-HT (500 micrograms, i.c.v.) plus metitepine (2 mg kg-1, s.c.) inhibited the gross behaviour and ACh release. ICS 205-930 (0.5 mg kg-1) prevented these responses. 5. 2-Methyl-5-HT, up to 10 mumols 1(-1), and 8-OH-DPAT, up to 0.1 mumols 1(-1), (like 5-HT) did not change [3H]-choline efflux from cerebral cortex slices. 6. These results suggest that exogenous 5-HT and related selective agonists modulate guinea-pig cortical cholinergic structures through 5-HT1A and 5-HT3 receptors. The stimulation of 5-HT1A autoreceptors may lead to disinhibition of the cholinergic cells, tonically inhibited by the tryptaminergic control. Conversely, the stimulation of 5-HT3 receptors inhibits ACh release, possibly through an interneurone. No direct 5-HT modulation of the cholinergic nerve endings was found.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed1989

Effect of 5-hydroxytryptamine on [3H]-acetylcholine release from guinea-pig striatal slices.

1. The effect of 5-hydroxytryptamine (5-HT) on spontaneous and electrically-evoked tritium efflux was studied in guinea-pig caudate nucleus slices preloaded with [3H]-choline. 2. 5-HT, 10-300 mumol l-1, temporarily increased the spontaneous tritium efflux (as well as the endogenous acetylcholine (ACh) release) and, after 15 min perfusion, inhibited it. The facilitatory effect of 5-HT on spontaneous efflux was increased while the inhibitory effect did not occur in slices taken from dopamine-depleted guinea-pigs. 3. The increase in spontaneous tritium efflux by 5-HT was blocked by methiothepin, methysergide (pA2 8.7) and by the selective 5-HT2 antagonist, ritanserin (pA2 6.7). 4. The inhibition of spontaneous tritium efflux by 5-HT was prevented by methysergide and methiothepin but not by ritanserin and (-)-propranolol. 5. 5-HT, 100 mumol l-1, inhibited the electrically-evoked tritium efflux and this effect was unchanged in dopamine-depleted slices. 6. The inhibition of electrically-evoked tritium efflux by 5-HT was blocked by methiothepin and methysergide but not by (-)-propranolol or ritanserin. 7. These results suggest that 5-HT may exert a rapid and transient (excitatory) and a more prolonged (inhibitory) control over striatal cholinergic neurones.

Acetylcholine↗
PubMed1988

Effect of ethylketocyclazocine on acetylcholine release in guinea-pig brain slices.

The effect of ethylketocyclazocine (EKC) on 3H-Choline (Ch) efflux and on endogenous acetylcholine (ACh) release from guinea-pig brain slices was studied. The drug inhibited the 3H-Ch efflux at a low concentration (0.1 mumol/l) in thalamus slices, while only at high concentrations (30-100 mumol/l) did EKC induce deep inhibition in the caudate nucleus and slight reduction in the cerebral cortex. Dynorphin (1-13) and morphine (Mo) inhibited the ACh release from thalamus slices as well. Naloxone (Nx) was more effective in antagonizing Mo than EKC. The experiments carried out with the endogenous ACh bioassay technique confirmed the above results. Mr 2266 and Mr 1452, both proposed as preferential k antagonists, per se enhanced 3H-Ch efflux from thalamus slices, while the dextrorotatory isomer Mr 1453, devoid of opioid properties, did not share such action. The role of k-opioid receptors in cholinergic system modulation in the guinea-pig brain is discussed.

Acetylcholine↗
PubMed1987

Influence of N-allyl-normetazocine on acetylcholine release from brain slices: involvement of muscarinic receptors.

The effects of (+/-)N-allyl-normetazocine on the release of acetylcholine from different areas of guinea-pig and rat brain were investigated. 1. The drug did not modify the electrically (2 Hz) evoked tritium efflux from guinea-pig cerebral cortex, thalamus and caudate nucleus slices, preloaded with 3H-choline 0.1 mumol/l and superfused with Krebs solution containing hemicholinium-3 10 mumol/l. 2. (+/-)N-allyl-normetazocine 10 mumol/l enhanced the evoked 3H efflux from guinea-pig brain slices superfused with Krebs solution containing physostigmine 30 mumol/l or oxotremorine 0.3-1 mumol/l; the effect was naloxone-insensitive and was abolished by atropine 0.15 mumol/l, but not by pirenzepine 1 mumol/l. 3. (+/-)N-allyl-normetazocine 5 mumol/l enhanced the electrically evoked release of endogenous acetylcholine as well, in a naloxone-insensitive way. 4. Both (+/-) and (+)N-allyl-normetazocine were without effect on 3H efflux from rat caudate nucleus slices electrically stimulated at 0.2 Hz frequency, after preloading with 3H-choline and during superfusion with hemicholinium-3. 5. The results are discussed in view of the antimuscarinic properties of the drug.

Acetylcholine↗
PubMed1986

The influence of 5-hydroxytryptamine on the release of acetylcholine from guinea-pig brain ex vivo and in vitro.

The effect of 5-hydroxytryptamine (5-HT) on the release of acetylcholine (ACh) from the brain of the guinea-pig was investigated in order to determine whether this amine plays a modulatory role on the cortical cholinergic projections. 5-Hydroxytryptamine (0.2-1 mumol), injected intracerebroventricularly (i.c.v.), caused mild excitation, stereotyped movements and ataxia. Simultaneously, it increased the output of ACh from the cortex in a dose-dependent manner. Methysergide (4.2 mumol Kg-1 i.p.) also increased the output of ACh by about 60-80%, but prevented the effect of 5-HT (1 mumol i.c.v.). Metitepine (1-4.2 mumol kg-1 i.p.) increased the output of ACh like methysergide but it changed the facilitation of the release of ACh by 5-HT into inhibition. At the same time the animals became hypothermic, sedated and their electroencephalogram (EEG) was synchronized. Pretreatment with 5,7-HT blocked the increase in release of ACh produced by 5-HT (1 mumol). D-Norfenfluramine (10.4 mumol kg-1) was ineffective alone but reduced the release of ACh in metitepine-pretreated animals. 5-Hydroxytryptamine (10-30 microM) did not affect the efflux of [3H]choline from electrically-stimulated slices of cerebral cortex. The increase in the release of ACh caused by 5-HT, abolished by pretreatment with methysergide and 5,7-HT, may be explained by activation of 5-HT autoreceptors, while the increase of transmitter outflow induced by methysergide may be due to a blockade of 5-HT receptors present on the cholinergic neurones. Metitepine appeared to unmask the tryptaminergic inhibition caused by injection of 5-HT intraventricularly or by the 5-HT-releasing drug, D-norfenfluramine, possibly by acting on the autoreceptors and preventing auto-inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

5,7-Dihydroxytryptamine↗
PubMedDate not supplied

Effect of opioid antagonists on acetylcholine release from guinea-pig brain slices: influence of peptidase inhibition.

With the aim of ascertaining the existence of an endogenous opioid control on cholinergic structures, the effects of the opioid antagonists naloxone, Mr 1452, Mr 2266, and ICI 174864 on spontaneous and electrically evoked [3H]choline (Ch) efflux from guinea-pig brain slices were tested. In cerebral cortex and caudate nucleus slices, no drug changed either resting or stimulus-evoked 3H-Ch efflux whether in the absence or in the presence of peptidase inhibitors (thiorphan 0.3 microM, bestatin 10 microM, captopril 10 microM, l-leucyl-l-leucine 2 mM). Conversely, in thalamus slices, the benzomorphan opioid antagonists Mr 1452 and Mr 2266 (but not their non-opioid stereoisomers Mr 1453 and Mr 2267) dose dependently increased St2/St1 ratios, when applied 15 min before St2 to slices superfused with normal Krebs solution. Peptidase inhibition potentiated the facilitatory effect of Mr compounds. Peptidase inhibitors per se reduced the stimulus evoked efflux of 3H-Ch, when present either from the beginning or from 15 min before St2 and potentiated the inhibition induced by dynorphin (Dyn). Mr 2266 fully antagonized any inhibitory effect induced by peptidase inhibitors, Dyn or their combination. ICI 174864, a selective delta antagonist, did not affect 3H-Ch efflux, while naloxone showed a tendency to increase it when peptidases were inhibited. Taken together, these data suggest the existence of an endogenous opioid tone inhibiting acetylcholine release in the guinea-pig thalamus. The relative affinities of the antagonists used suggest that the receptor involved may be of the kappa type.

Acetylcholine↗
PubMedDate not supplied

Induction of epileptiform activity by temperature elevation in hippocampal slices from young rats: an in vitro model for febrile seizures?

Extracellular field potential recordings were performed in the CA1 subfield of hippocampal slices obtained from Wistar rats aged 2-38 days. When the brain tissue was maintained at 35 degrees-36 degrees C (values obtained in the tissue chamber well), single-shock orthodromic stimuli elicited a response in the stratum pyramidale that consisted of a single population spike. In contrast, when the temperature in the well was increased to levels greater than 38.2 degrees C for periods of 5-15 min, the same type of stimuli elicited an epileptiform response characterized by a 250- to 600-ms-long, positive-going field potential with superimposed, multiple, negative-going population spikes. This potential resembled the epileptiform response recorded in the hippocampal slice in the presence of convulsants such as penicillin or bicuculline. Once the temperature was restored to control values (i.e., 35 degrees-36 degrees C) after induction of epileptiform activity, the abnormal response could be observed for less than or equal to 2 h. In some experiments (approximately one third of the successful trials), spontaneous epileptiform discharges appeared during and persisted after the increase in temperature. The ability of the hyperthermic period to induce epileptiform changes was age dependent: Epileptiform activity outlasting the period of temperature elevation was not observed in slices obtained from rats aged less than 4 days or greater than 28 days. Our data show that epileptiform activity can be induced by a transient increase in temperature and that the age of the animals from which slices are obtained plays an important role in the appearance of this phenomenon.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗