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L Beani

Publications and source records attributed to L Beani.

At least 55 records · Page 3Linked to original sources
PubMed1997

Characterization of glutamate and [3H]D-aspartate outflow from various in vitro preparations of the rat hippocampus.

The characteristics of high-K+ and electrically evoked endogenous glutamate and [3H]D-aspartate release have been studied in multiple in vitro preparations of the rat hippocampus (transverse slices, granule cells cultures, synaptosomes and mossy fibre synaptosomes) under similar experimental conditions. High external K+ concentrations evoked [3H]D-aspartate and endogenous glutamate overflow in a concentration-dependent manner in all preparations (except it was not possible to measure endogenous glutamate outflow from granule cells). This effect was tetrodotoxin-insensitive but partially calcium-dependent. In slices, field electrical stimulation evoked an overflow of endogenous glutamate, but not of [3H]D-aspartate, in a frequency-dependent manner. This effect was concentration-dependently amplified by the glutamate uptake inhibitor L-trans-pyrrolidine-2,4-dicarboxylic acid (t-PDC). The electrically evoked glutamate overflow in the presence of t-PDC was tetrodotoxin-sensitive and calcium-dependent. In primary dentate gyrus cell cultures, electrical stimulation evoked an overflow of [3H]D-aspartate in a frequency-dependent manner, while endogenous glutamate outflow was not detectable. This effect could be inhibited by tetrodotoxin and by the N-type calcium channel blocker omega-conotoxin GVIA. Finally, the effect of adenosine has been studied in order to assess the pharmacological modulability of [3H]D-aspartate and endogenous glutamate stimulation-induced overflow. Adenosine was found to inhibit 35 mM K(+)- and 20 Hz electrical stimulation-induced [3H]D-aspartate and endogenous glutamate overflow. These effects were all prevented by the A1 receptor antagonist 8-cyclopentyl-1,3-dimethylxanthine (CPT). These data are in line with the hypothesis that reuptake plays a role in regulating glutamate release, and that [3H]D-aspartate represents a valid marker of endogenous glutamate under most (but not all) experimental conditions.

Adenosine↗
PubMed1997

Post-ischemic recovery of acetylcholine release in vitro: influence of different excitatory amino acid receptor subtype antagonists.

The release of endogenous acetylcholine was measured in electrically (5-20 Hz) stimulated guinea pig cerebral cortex and caudate nucleus slices under ischemic (hypoxic and glucose-free) conditions. Ischemia reduced acetylcholine release by 40-90%; the inhibition depended on the duration of ischemia (10-30 min) while the extent of post-ischemic recovery was inversely related to it. Caudate nucleus slices displayed a higher sensitivity to ischemia than did cortical slices. To test the effects of excitatory amino acid receptor antagonists on the ischemia-induced reduction of acetylcoline release and on its post-ischemic recovery, the following drugs were used: 5-methyl-10,11-dihydro-5-H-dibenzo-[a,b]-cyclohepten-5,10-imine (MK-801,-a blocker of the N-methyl-D-aspartate [NMDA] receptor-linked channel), 7-chloro-kynurenic acid (7-Cl-KYN) and (E)-3-[2(phenylcarbamoyl)ethenyl]-4,6-dichloroindole-2-carboxylic acid sodium salt (GV150526A, blockers of the glycine site of the NMDA receptor), eliprodil, (an antagonist at the polyamine site of the NMDA receptor), and 6-cyano- 7-nitro-quinoxalin-2,3-dione (CNQX, a D,L-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionic acid [AMPA] receptor antagonist). These did not modify the time-course and the extent of ischemia-induced inhibition but improved post-ischemic recovery in a concentration dependent manner. GV 150526A and CNQX appeared to be more effective in the cerebral cortex. Only eliprodil was devoid of any effect in both areas. The evaluation of acetylcholine release from brain slices represents a suitable in vitro model to quantify the effectiveness of drugs in favouring recovery from the cholinergic presynaptic failure induced by ischemic conditions. The different effects of the excitatory amino acid receptor antagonists cited above, depending on the brain areas considered and the receptor subtypes involved, may be of interest in view of their therapeutic potential.

Acetylcholine↗
PubMed1997

Inhibitory cholinergic control of endogenous GABA release from electrically stimulated cortical slices and K(+)-depolarized synaptosomes.

In the present study we characterize the optimal experimental conditions under which to investigate the cholinergic regulation of endogenous electrically evoked gamma-aminobutyric acid (GABA) release from guinea pig cortical slices. Superfusion with the neuronal GABA reuptake inhibitor, SKF89976A (10 microM) caused cortical GABA release to be linearly correlated with the frequency of electrical stimulation (5, 10, 20 Hz). Electrically evoked GABA release (10 Hz) was tetrodotoxin-sensitive and Ca(2+)-dependent and was under GABAB autoreceptor control. Under these experimental conditions, acetylcholine (0.1-10 microM) and physostigmine (30 microM) decreased the electrically evoked GABA release while the M2 receptor antagonist AFDX-116 (0.01-0.1 microM) counteracted these effects. Similar results were also observed in a cortical synaptosomal preparation stimulated with K+ (10 mM). These findings demonstrate an inhibitory cholinergic regulation of electrically evoked GABA release via M2 receptors located on cortical GABAergic terminals.

Acetylcholine↗
PubMed1996

Connections of the dorsomedial part of the nucleus intercollicularis in a male non-songbird, the Grey partridge: a tract-tracing study.

Vocal control systems have been poorly investigated in non-songbirds. In this study we describe descending neural pathways to the dorsomedial portion of the nucleus intercollicularis (ICo) in a galliform (male Grey partridges) by means of the DiI in vitro tracing technique. The simple and sex-dimorphic vocalizations of partridges, which have a critical role in sexual selection, favour this species as a model system for the study of vocal control mechanisms. Our data demonstrate that the ICo, an important site mediating the activation of vocal behavior in all birds, receives afferents from several important higher centers: the nucleus pretectalis, the tuberoinfundibular hypothalamic region, the dorsal thalamus, the preoptic region and the paleostriatal region. Efferent connections of the ICo were directed mainly to the hypothalamic area. This complex neural pathway is consistent with a major role of ICo in male courtship and vocal performance control.

Animals↗
PubMed1996

Biotin deficiency facilitates kindling hyperexcitability in rats.

Biotin-deficient conditions are frequently associated with epileptic disorders. Biotin deficiency may be caused by long-term treatment with anticonvulsants or excessive ingestion of avidin. Absence of biotinidase activity can also lead to biotin deficiency, and is characterized by developmental delay as well as neurological and dermatological abnormalities. Because seizures are one of the most frequent signs of the latter, biotin-deficient conditions could conceivably facilitate convulsive disorders. To test this hypothesis, we investigated the occurrence of a latent kindling hyperexcitability in biotin-deprived rats. In these animals, duration of after-discharge on the first stimulation was longer at threshold amplitude, kindling development through its early stages was accelerated and duration of the forelimb clonus of fully kindled seizures was increased. Biotin deprivation in mixed cerebellar granule cell-astrocyte cultures also produced a tetrodotoxin-sensitive delayed loss of the glutamatergic neuronal population. The data thus support a facilitatory role for biotin-deficient conditions in convulsive disorders.

Animals↗
PubMed1996

Evidence for an in vivo and in vitro modulation of endogenous cortical GABA release by alpha-glycerylphosphorylcholine.

The effects of alpha-glycerylphosphorylcholine (alpha-GPC) on endogenous cortical GABA release were studied both in vivo and in vitro. In freely moving rats, equipped with epidural cups, alpha-GPC (30-300 mg/kg i.p.) increased GABA release. This effect was potentiated by atropine, both systematically administered (5 mg/kg i.p.) and locally applied (1.4 microM), but not by mecamylamine (4 mg/kg i.p.). The alpha-GPC-induced increase in GABA release was abolished in rats pretreated with the alpha 1 receptor antagonist prazosin (14 micrograms/kg i.p.). In cortical slices alpha-GPC (0.4 mM) increased the spontaneous GABA efflux. This effect was abolished by tetrodotoxin (0.5 microM) and prazosin (1 microM), but not by atropine (0.15 microM) or mecamylamine (2.5 microM). These results indicate that the facilitatory response by alpha-GPC on GABA release does not depend on a direct activation of either muscarinic or nicotinic receptors, but suggest the involvement of the noradrenergic system.

Animals↗
PubMed1996

Post-hypoxic recovery of acetylcholine release: different sensitivity of guinea pig neocortical and striatal slices.

The release of endogenous acetylcholine (ACh) was measured in superfused guinea-pig cortical and striatal slices, kept at rest or electrically stimulated at different frequencies, before and during severe hypoxic conditions as well as after reoxygenation. In the cortex the basal release was unchanged by 30-60 min of hypoxia while it was inhibited in the striatum. The release evoked by short-term (2 min) stimulation at 0.5 Hz was moderately reduced (to 76%) by 30 min hypoxia in the cortex and in the striatum, but fully recovered after reoxygenation. The release evoked by continuous stimulation (from 5 to 10 to 20 Hz) was strongly inhibited (to 12-30%) in both areas after 30 min of hypoxia. After 30 min of reoxygenation, the recovery was complete in the cortex (mainly provided with cholinergic axons), but it was incomplete in the striatum (rich in cholinergic interneurones). The extent of the recovery in the latter area (i) was inversely related to stimulation frequency, (ii) did not depend on the depletion of neurotransmitter stores, because ACh tissue levels were fully restored by reoxygenation, and (iii) was consistently facilitated by excitatory aminoacid antagonists, slightly improved by the adenosine agonist R-phenylisopropyladenosine and unaffected by reducing the concentrations of radical species with catalase and superoxide dismutase or N omega-nitro-L-arginine. These results emphasize (i) the different vulnerability of the cortical and striatal cholinergic structures, (ii) the high sensitivity of the striatal interneurones to the frequency of stimulation during the posthypoxic recovery, and (iii) the relevant role played by endogenous glutamate on activity-dependent neurosecretory failure.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1996

Evidence for a differential cholecystokinin-B and -A receptor regulation of GABA release in the rat nucleus accumbens mediated via dopaminergic and cholinergic mechanisms.

In the present study we characterized the cholecystokinin receptor regulation of (i) the dopamine D2 agonist binding sites in striatal sections including the nucleus accumbens and (ii) GABA and dopamine release in the central part of the rat nucleus accumbens, by combining the in vitro filter wipe-off and the in vivo microdialysis techniques. In the binding study we demonstrate that sulphated cholecystokinin octapeptide (1 nM) increased (219 +/- 30%) the KD value of the D2 agonist [3H]N-propylnorapomorphine binding sites in sections from the striatum including the accumbens. This effect was counteracted by the cholecystokinin-B antagonist PD134308 (50 nM). In a parallel study using microdialysis in the central nucleus accumbens, we found that local perfusion with sulphated cholecystokinin octapeptide (1 microM) induced an increase in GABA (135 +/- 7%) and dopamine (146 +/- 8%) release which was unaffected by the cholecystokinin-A antagonist L-364,718 (10 nM). In contrast, when the cholecystokinin-B antagonist PD134308 (10 nM) was co-perfused with the peptide it prevented the increase in dopamine and decreased GABA release (-24 +/- 2%). This reduction was counteracted by the addition to the perfusate medium of the cholecystokinin-A antagonist or the cholinergic muscarinic M2 receptor antagonist AF-DX 116 (0.1 microM). Taken together, these data demonstrate that the facilitation by sulphated cholecystokinin octapeptide of GABA and dopamine release in the central accumbens probably reflects an inhibitory effect of the peptide on both pre- and postsynaptic D2 receptors, mediated via cholecystokinin-B receptor activation. In addition, for the first time we provide evidence for a differential cholecystokinin-A and -B receptor-mediated regulation of GABA transmission in the central accumbens, where the cholecystokinin-B receptor exerts a dominant excitatory influence while the cholecystokinin-A receptor mediates an inhibition of GABA release via a local muscarinic M2 receptor.

Animals↗
PubMed1996

Kindled seizure-induced c-fos and prodynorphin mRNA expressions are unrelated in the rat brain.

Levels of mRNA for c-fos and prodynorphin were studied by in situ hybridization in adjacent coronal sections taken from kindled rats 30-60 min after the last seizure. Within this time frame, expression of both genes was induced in multiple brain areas. Anatomical colocalization of the induced gene expressions was found in the hippocampus. Induction of c-fos in the dentate gyrus was bilateral and symmetrical in a subgroup of rats, ipsilateral in another subgroup and absent in a third subgroup. However, no relative increase was observed in the ipsilateral compared with the contralateral prodynorphin expression in the dentate gyrus when c-fos expression was induced ipsilaterally only. These observations suggest that, at variance with other experimental situations, Fos is not involved in the mechanisms of kindled seizure-induced activation of prodynorphin transcription in the rat forebrain.

Animals↗
PubMed1995

Early changes in prodynorphin mRNA and ir-dynorphin A levels after kindled seizures in the rat.

Prodynorphin mRNA and immunoreactive dynorphin A (ir-dynorphin A) levels were measured in different brain areas at various time points after amygdala kindled seizures. In the hippocampus, striatum and hypothalamus, prodynorphin mRNA levels were not significantly changed in kindled rats (killed 1 week after the last stimulus-evoked seizure), but they were significantly increased 1 h after seizures. The relative increase was the highest in the hippocampus (approximately 3-fold). In the brainstem, midbrain and cerebral cortex no changes in prodynorphin mRNA were detected in kindled rats, 1 h or 1 week after a kindled seizure. ir-Dynorphin A levels were significantly reduced in the hippocampus and in the striatum of kindled rats, as well as 5 and 60 min after kindled seizures, but they were increased back to control levels after 120 min. In the hypothalamus, ir-dynorphin A levels were significantly increased 120 min after a kindled seizure. ir-Dynorphin A levels were also significantly reduced in the brainstem and in the frontal, parietal and temporal cortex 120 min, but not 5 or 60 min, after a kindled seizure. Taken together, these data support the hypothesis that the dynorphinergic system is activated after amygdala kindled seizures, with different kinetics in different brain areas.

Amygdala↗
PubMed1995

Modafinil and cortical gamma-aminobutyric acid outflow. Modulation by 5-hydroxytryptamine neurotoxins.

The acute or chronic administration of modafinil, (diphenyl-methyl-sulfinyl-2-acetamide, 30 mg/kg s.c.) decreased gamma-amino-butyric acid (GABA) outflow from the cerebral cortex of freely moving guinea pigs and rats. In 5,7-dihydroxytryptamine intracerebroventricularly pretreated guinea pigs, the effect of modafinil on GABA outflow was reversed and the noradrenaline cortical levels increased. Prazosin (35.8 ng/kg i.p.) blocked the drug-induced increase in GABA efflux. In vitro experiments, performed in rat cortical slices, showed that modafinil failed to affect [3H]GABA release and uptake as well as glutamic acid decarboxylase activity. In conclusion, our results suggest that the balance between central noradrenaline and 5-hydroxytryptamine transmission is important for the regulation by modafinil of the GABAergic release in the cerebral cortex.

5,7-Dihydroxytryptamine↗
PubMed1995

Testosterone-induced changes of call structure, midbrain and syrinx anatomy in partridges.

Testosterone (T) treated Grey partridges (Perdix perdix) of both sexes uttered significantly longer and lower-pitched calls than controls; both these acoustic features play a critical role in mate choice. A morphometrical analysis of the midbrain nucleus intercollicularis showed a cell size increase in T-treated birds regardless of their sex. Histological study of the syrinx did not reveal any sexually dimorphic structure in experimental and control birds; the major T-induced change was a thickening of the external membranes, reported to be the main sound source in Galliforms. In conclusion, T appears able to modify not only some acoustic parameters, but also certain anatomical structures at the peripheral and central levels of the vocal system in a nonoscine species.

Animals↗
PubMed1995

AMPA receptor activation regulates the glutamate metabotropic receptor stimulated phosphatidylinositol turnover in human cerebral cortex slices.

The effect of excitatory amino acids (EAA) on phosphatidylinositol (PI) turnover in human cerebral cortical slices was investigated. Trans-1-aminocyclopentane-1,3-dicarboxylic acid (ACPD) increased inositol phosphate (IP) formation in the 1-1000 microM range. Quisqualic acid (QA) was maximally effective at 10-100 microM, showing an inverse correlation between concentration and effect in the 100-1000 microM range. The glutamate metabotropic receptor antagonist 2-amino-3-phosphonopropionic acid (AP3), the ionotropic non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) and the NMDA channel blocker dizolcipine (MK-801) failed to prevent the PI response to ACPD (1000 microM). However, CNQX (100 microM) modified the concentration-response curve of QA reducing the effect of QA 10 microM by approx. 50% and enhancing that of QA 1000 microM by 2-fold. In addition, CNQX (100 microM) together with MK-801 (100 microM) unmasked the ability of L-glutamate (L-GLU) 3000 microM to stimulate PI turnover. The effect of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) on the EAA-induced PI turnover was also studied. AMPA (0.1-1 microM) potentiated the response to submaximal (30 microM) ACPD and (1 microM) QA concentrations. However, higher AMPA concentrations (10 microM) failed to synergize with ACPD 30 microM and, in addition, inhibited the PI turnover maximally stimulated by QA 10 microM. These results further support the presence of the glutamate metabotropic receptor in the human neocortex. In addition, they show the occurrence of a concentration-related dual interaction between AMPA and glutamate metabotropic receptor activation in the IP formation in this brain area.

6-Cyano-7-nitroquinoxaline-2,3-dione↗
PubMed1995

Changes in [3H]-UK 14304 binding to alpha 2-adrenoceptors in morphine-dependent guinea-pigs.

1. The aim of this study was to investigate the effect of a noradrenergic input in the cortex of morphine-dependent animals. Binding of the alpha 1-adrenoceptor ligand [3H]-prazosin did not change in cortical membranes taken from morphine-dependent as compared to control guinea-pigs. However, binding of the alpha 2-adrenoceptor ligand [3H]-UK 14304 showed decreased KD (-30%) in the absence of significant changes in Bmax, either in cortical membranes or in synaptosomes. 2. Several characteristics of this phenomenon were identified. First, it occurs in a time-dependent fashion, in that it takes 5 days of chronic morphine treatment to start developing. Second, it can be observed after acute administration of high doses of morphine (100 mg kg-1). Third, it does not require a connection with the locus coeruleus or with other subcortical structures, in that it can be reproduced in vitro in isolated cortical slices. Fourth, it requires the integrity of cortical structures, since it cannot be reproduced in vitro in cortical synaptosomes. 3. Release studies were run to attempt identification of a functional correlate of the above observations. No changes were observed in the ability of the alpha 2-adrenoceptor agonist UK 14304 to inhibit 35 mM K(+)-evoked [3H]-noradrenaline outflow from cortical synaptosomes taken from morphine-dependent as compared to control guinea-pigs. However, a large decrease in the IC50 of UK 14304 for the inhibition of 35 mM K(+)-evoked [3H]-gamma-aminobutyric acid ([3H]-GABA) outflow (41 vs. 501 nM) was observed in morphine-dependent as compared to control animals. 4. These data suggest that, in the guinea-pig, chronic morphine treatment is associated with a shift from a low to high affinity agonist state in alpha 2-adrenoceptors on cortical GABA terminals.

Adrenergic alpha-Agonists↗
PubMed1995

5-Hydroxytryptamine-mediated effects of nicotine on endogenous GABA efflux from guinea-pig cortical slices.

1. The effect of nicotine on endogenous basal GABA outflow was studied in guinea-pig cerebral cortex slices. 2. Nicotine 1.86-18.6 mumol l-1 significantly decreased the basal, tetrodotoxin-sensitive GABA efflux, whereas at higher concentrations (186-620 mumol l-1) nicotine increased it. The inhibition was prevented by mecamylamine while the facilitation was blocked by mecamylamine, (+)-tubocurarine and tetrodotoxin. 3. The effect of nicotine was due to an indirect 5-hydroxytryptaminergic action. In fact, MDL 72222 (1 mumol l-1) completely prevented the alkaloid inhibition and methysergide (1 mumol l-1) reversed the facilitation into inhibition; concomitant treatment with methysergide and MDL 72222 antagonized the effect of nicotine at 186 mumol l-1 4. Lower concentrations of 5-HT (3-10 mumol l-1) decreased, whereas higher concentrations (30-100 mumol l-1) increased, spontaneous GABA outflow. The inhibition of GABA efflux was prevented by MDL 72222 whereas the facilitation was reversed by methysergide (1 mumol l-1) into inhibition, and prevented by MDL 72222 1 mumol l-11. 5. These results suggest that, by activating nicotinic receptors present on 5-hydroxytryptaminergic terminals, nicotine releases 5-HT which, in turn, inhibits or increases the secretory activity of cortical GABA interneurones via 5-HT3 and methysergide-sensitive receptors, respectively.

Animals↗
PubMed1994

Adenosine A1 receptors in the rat brain in the kindling model of epilepsy.

Adenosine and adenosine analogues have potent anticonvulsant effects on various seizure models, including kindling, an animal model of temporal lobe epilepsy. It is now reported that binding of a specific ligand (cyclohexyladenosine) to adenosine A1 receptors is not changed in the cerebral cortex of kindled rats. However, the affinity of cyclohexyladenosine to adenosine receptors is significantly increased in the hippocampus. In addition, cyclohexyladenosine is slightly more potent to inhibit [3H]D-aspartate outflow from hippocampal synaptosomes taken from kindled than from control rats. Taken together, these data suggest that an increased affinity of adenosine to A1 receptors may play a role in the anticonvulsant effect of adenosine A1 analogues in the kindling model.

Adenosine↗
PubMed1994

Monoamines modulate the electrically-evoked efflux of 3H-choline from slices of guinea pig nucleus basalis magnocellularis.

The influence exerted by monoamines on acetylcholine release was studied in electrically stimulated slices of guinea pig nucleus basalis magnocellularis (nbM) prelabelled with 3H-choline (3H-Ch). Noradrenaline, 30 microM, and clonidine, 1 microM, reduced the evoked 3H-Ch efflux by about 50%, but phenylephrine, 100 microM, did not; idazoxan, 0.1 microM, but not prazosin, 1 microM, antagonized these effects, pointing to the involvement of alpha 2 receptors. Apomorphine, 1 or 30 microM, reduced 3H-Ch efflux from nbM slices as well. The effect was shared by quinpirole, 1 or 10 microM, but not by 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (SKF 38393), 10 microM, and was antagonized by sulpiride, 1 microM, but not by R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3-benzazepin++ +-7-ol (SCH 23390), 1 microM, suggesting the involvement of the D2 receptor subtype. 5-hydroxytryptamine (5-HT) 0.3-30 microM, and alpha-methyl-5-HT, 10 microM, significantly increased 3H-Ch efflux from nbM slices; the 5-HT2 antagonist ritanserin, 1 microM, prevented this response. 2-methyl-5-HT, 1-30 microM, inhibited the evoked 3H-Ch efflux and its effect was prevented by the 5-HT3 antagonist 1 alpha H,3 alpha,5 alpha H-tropan-3-yl-3,5-dichlorobenzoate (MDL 72222), 1 microM. These findings indicate that i) catecholamines inhibit nbM neurons through alpha 2 and D2 receptors and that ii) a complex serotonergic modulation of cholinergic function exists in the nbM, involving the activation of various receptor subtypes, which can mediate opposite responses.

Acetylcholine↗