Biomedical subjects

L Beani

Publications and source records attributed to L Beani.

At least 19 recordsLinked to original sources

PubMed2000

Nicotinic modulation of [(3)H]D-aspartate outflow from cultured cerebellar granule cells.

The effect of nicotine on basal and electrically evoked (20 Hz for 20 sec) [(3)H]D-aspartate efflux (assumed as an index of transmitter release) was studied in rat cerebellar granule primary cultures. Nicotine (10-100 nM) increased the basal efflux two to three times and concentration-dependently enhanced the electrically evoked efflux up to ten times. Higher drug concentration (1 microM) underwent rapid desensitization. Facilitation of the efflux was similarly reduced by the nicotinic acetylcholine receptor antagonists, alpha-bungarotoxin and mecamylamine, suggesting the involvement of at least two receptor subtypes containing and lacking alpha(7) subunits, respectively. Since the increased efflux induced by nicotine in granule cells kept at rest or depolarized by KCl 15 mM was antagonized by tetrodotoxin, the involvement of sodium channels by receptors located at preterminal sites was suggested. Taken together, these findings emphasize the role of the cholinergic input in granule cell function and in glutamatergic signaling.

Acetylcholine↗

PubMed2000

The nicotinic modulation of [(3)H]D-aspartate outflow in primary cultures of rat neocortical neurons: effect of acute and long term nicotine treatment.

The effect of nicotine 1 nM-10 microM on the efflux of [(3)H]D-aspartate was tested in primary cultures of rat cortical neurons kept at rest and subjected to electrical field stimulation. Two trains of pulses at 20 Hz for 20 s were applied at the 60th (St(1)) and 90th (St(2)) min of perfusion. The drug slightly and transiently increased the efflux of resting cells while, when given during St(2), it greatly enhanced the electrically evoked efflux estimated as St(2)/St(1) ratio, EC(50) being 107 nM. The nicotinic receptors (nAChR) giving rise to this positive modulation were partly mecamylamine- and partly alpha-bungarotoxin-sensitive. They appeared to be located at the nerve endings since nicotine facilitation was only slightly prevented by tetrodotoxin during depolarisation with 15 mM KCl. Pretreatment with glutamate antagonists did not reveal any interaction between nAChR and ionotropic glutamate receptors. Membrane glutamate carrier involvement in the nicotine effect was ruled out. Long-term treatment with nicotine 1 microM (from the 3rd-4th to the 8th-9th day in vitro) reduced the maximal response to the drug but shifted its threshold concentration to the left (from 10 nM to 1 nM), leaving the contribution of the two receptor subtypes unchanged. Reduced responsiveness to nicotine was also evident in long-term treated cerebellar granule cells. In conclusion, presynaptic nAChR's, both containing and lacking alpha(7) subunits, can contribute to enhance the glutamatergic secretion in primary cultures of rat cortical neurons, chiefly during electrical stimulation.

Acetylcholine↗

PubMed2000

High sensitivity bioassay of paralytic (PSP) and amnesic (ASP) algal toxins based on the fluorimetric detection of [Ca(2+)](i) in rat cortical primary cultures.

A high sensitivity bioassay able to recognise small amounts of paralytic and amnesic toxins in algal acetic extracts is described. The method is based on the measure of intracellular [Ca(2+)](i) in primary cultures of rat cortical neurones preloaded with Fura-2 and submitted to electrical field stimulation. Under normal conditions the basal [Ca(2+)](i) level was about 50-100 nM and was nearly doubled during the peaks induced by trains of electrical pulses at 10 Hz for 10 s. Saxitoxin (STX) 3.5 nM and tetrodotoxin (TTX) 24 nM halved the peaks height without affecting basal [Ca(2+)](i). Conversely, domoic acid increased the basal [Ca(2+)](i) (EC(50)=3. 7 microM) and decreased the calcium peaks (EC(50)=7.3 microM). CNQX (a competitive antagonist of AMPA/KA receptors) at 10 microM shifted to the right by a factor of 3 the concentration-response curves of domoic acid. The extracts of non-toxic algae were well tolerated by up to 10 microg protein/ml, whereas extracts of Alexandrium lusitanicum at 1-4 microg protein/ml reduced [Ca(2+)](i) peaks and increased basal calcium levels. This toxic effect of A. lusitanicum was unexpected since parallel HPLC analysis showed only the presence of gonyautoxins, known to act like saxitoxin. Therefore, the bioassay on rat cortical neurones revealed a complex composition of the toxins present in A. lusitanicum. The relevance of fluorimetric detection of [Ca(2+)](i) in primary neuronal cultures in the evaluation of algal risk is stressed.

Algal Proteins↗

PubMed2000

Modulation of 5-hydroxytryptamine efflux from rat cortical synaptosomes by opioids and nociceptin.

The modulation of [(3)H]-5-hydroxytryptamine ([(3)H]-5-HT) efflux from superfused rat cortical synaptosomes by delta, kappa, mu and ORL(1) opioid receptor agonists and antagonists was studied. Spontaneous [(3)H]-5-HT efflux was reduced (20% inhibition) by either 0.5 microM tetrodotoxin or Ca(2+)-omission. Ten mM K(+)-evoked [(3)H]-5-HT overflow was largely Ca(2+)-dependent (90%) and tetrodotoxin-sensitive (50%). The delta receptor agonist, deltorphin-I, failed to modulate the K(+)-evoked neurotransmitter efflux up to 0.3 microM. The kappa and the mu receptor agonists, U-50,488 and endomorphin-1, inhibited K(+)-evoked [(3)H]-5-HT overflow (EC(50)=112 and 7 nM, respectively; E(max)=28 and 29% inhibition, respectively) in a norBinaltorphimine- (0.3 microM) and naloxone- (1 microM) sensitive manner, respectively. None of these agonists significantly affected spontaneous [(3)H]-5-HT efflux. The ORL(1) receptor agonist nociceptin inhibited both spontaneous (EC(50)=67 nM) and K(+)-evoked (EC(50)=13 nM; E(max)=52% inhibition) [(3)H]-5-HT efflux. The effect of NC was insensitive to naloxone (up to 10 microM), but was antagonized by [Nphe(1)]nociceptin(1-13)NH(2) (a novel selective ORL(1) receptor antagonist; pA(2)=6.7) and by naloxone benzoylhydrazone (pA(2)=6.3). The ORL(1) ligand [Phe(1)psi(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) also inhibited K(+) stimulated [(3)H]-5-HT overflow (EC(50)=64 nM; E(max)=31% inhibition), but its effect was partially antagonized by 10 microM naloxone. It is concluded that the ORL(1) receptor is the most important presynaptic modulator of neocortical 5-HT release within the opioid receptor family. This suggests that the ORL(1)/nociceptin system may have a powerful role in the control of cerebral 5-HT-mediated biological functions.

Analgesics, Opioid↗

PubMed2000

Increased responsivity of glutamate release from the substantia nigra pars reticulata to striatal NMDA receptor blockade in a model of Parkinson's disease. A dual probe microdialysis study in hemiparkinsonian rats.

Dual probe microdialysis was employed in freely moving 6-hydroxydopamine (6-OHDA) hemilesioned rats to investigate the effects of blockade of N-methyl-D-aspartate (NMDA) receptors in the dorsolateral striatum on glutamate (Glu) release from the ipsilateral substantia nigra pars reticulata (SNr). Perfusion for 60 min with the NMDA antagonist dizocilpine (0.1 and 1 microM) in the dopamine (DA)-denervated striatum stimulated nigral Glu release (peak effect of 139 +/- 7% and 138 +/- 9%, respectively). The lower (0.01 microM) and higher (10 microM) concentrations were ineffective. In sham-operated rats, dizocilpine failed to affect nigral Glu release up to 1 microM but induced a prolonged stimulation at 10 microM (153 +/- 9% at the end of perfusion). The present results show that DA-deficiency in the striatum of hemiparkinsonian rats is associated with increased responsivity of nigral Glu release to striatal NMDA receptor blockade. This suggests that changes of NMDA receptor mediated control of the striatofugal pathways occur during Parkinson's disease (PD).

Animals↗

PubMed1999

5-HT4 receptor modulation of acetylcholine outflow in guinea pig brain slices.

The effect of the 5-HT4 agonist, BIMU-8 was studied on [3H]choline outflow in guinea pig brain slices and synaptosomes. BIMU-8 did not modify [3H]choline efflux in slices kept at rest, but increased [3H]choline outflow in electrically stimulated slices of cerebral cortex (CC), hippocampus (hip) and nucleus basalis magnocellularis (nbm). This effect was prevented by the selective 5-HT4 antagonist, GR 125487. Conversely, BIMU-8 did not affect [3H]choline efflux in hippocampal synaptosomes depolarized with KCl 20 mM. These results provide evidence that BIMU-8 increases the electrically triggered [3H]choline efflux in CC, hip and nbm slices. A possible role of 5-HT4 agonists in memory and learning diseases is suggested.

Acetylcholine↗

PubMed1999

Stripes display in hover-wasps (Vespidae: Stenogastrinae): a socially costly status badge.

During their daily patrols of their hover sites, male stenogastrine wasps display three white stripes on their tergites by fully stretching their abdomen. In captive Parischnogaster mellyi males, we observed a positive relationship between mating and both display frequency and successful aerial duels. Approaches of receptive females to hovering males and sexual interactions were most frequent at the end of the males' performance, when only a few individuals displayed their stripes in flight. We investigated the function and cost of the stripes display by manipulating this sex-dimorphic trait. Wasps with additional white stripes (simulating continuously displaying individuals) were pursued and touched more frequently by rivals, stopped their activity earlier than controls and foraged more intensely. Copyright 1999 The Association for the Study of Animal Behaviour.

Journal Article↗

PubMed1999

Changes in hippocampal and cortical B1 bradykinin receptor biological activity in two experimental models of epilepsy.

An increased response to the activation of receptors mediating excitatory effects may be involved in some forms of epilepsy. In this study, it has been tested whether B1 bradykinin receptors (which mediate excitatory effects in the peripheral nervous system and have little constitutional expression in the central nervous system) may be proposed in this role. Two experimental models of epilepsy (kindling and kainate) have been employed, and glutamate outflow experiments have been performed in hippocampal and cortical slices taken from control, kindled and kainate-treated rats. The endogenous B1 receptor agonist Lys-des-Arg9-bradykinin (10(-7) M) did not affect electrically-evoked glutamate overflow in control animals, but concentration-dependently increased it in kindled rats (maximal effect +40 to + 50%) and, to a lesser extent (+20%), in kainate-treated rats. These effects were fully prevented by the selective B1 receptor antagonist R-715 (10(-6) M), but not by the selective B2 receptor antagonist Hoe 140 (10(-6) M). The observed changes in B1 bradykinin receptor biological activity may play a role in epileptic hyperexcitability.

Animals↗

PubMed1999

Inhibitory effect of nociceptin on [3H]-5-HT release from rat cerebral cortex slices.

1. The effect of nociceptin (NC) on 5-hydroxytryptamine (5-HT) release was studied in rat cerebral cortex slices preincubated with [3H]-5-HT and electrically stimulated (3 Hz, for 2 min) at the 45th (St1) and the 75th (St2) min of superfusion. 2. NC (0.1 - 3 microM), present in the medium from the 70th min onward, concentration-dependently reduced electrically evoked [3H]-5-HT efflux (pEC50=6.54, Emax -54%). The inhibition was not antagonized by naloxone (1 microM) ruling out the involvement of opioid receptors. 3. Phe1psi(CH2-NH2)Gly2]NC(1-13)NH2, which acts as an opioid-like receptor (ORL1) antagonist at the peripheral level, behaved as a partial agonist in cerebral cortex slices i.e. it inhibited [3H]-5-HT efflux when added before St2, however, when present in the medium throughout the whole experiment, [Phe1psi(CH2-NH2)Gly2]NC(1-13)NH2 prevented the action of NC added at the 70th min. 4. The non-selective ORL1 receptor antagonist, naloxone benzoylhydrazone (3 microM), in the presence of 10 microM naloxone, did not modify the St2/St1 ratio but completely abolished the NC effect. 5. These findings demonstrate that NC inhibits 5-HT release from rat cerebral cortex slices via ORL1 receptors, suggesting its involvement in central processes mediated by 5-HT.

Animals↗

PubMed1999

In vitro evidence for increased facilitation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors in hemiparkinsonian rats.

The NMDA-evoked acetylcholine release from striatal slices and synaptosomes was investigated in rats subjected to unilateral injection of 6-hydroxydopamine into the substantia nigra. In slices prepared from the striatum contralateral to the lesion, the NMDA-evoked endogenous acetylcholine release was not significant at 10 microM NMDA and maximal at 100 microM NMDA (124 +/- 19%). Conversely, in slices taken from the dopamine-depleted striatum, NMDA was effective even at 10 microM (41 +/- 4%), and at 100 microM (196 +/- 24%) efficacy was nearly doubled. In synaptosomes prepared from the contralateral striatum, NMDA maximally stimulated 20 mM KCl-induced endogenous acetylcholine release at 1 microM (66 +/- 5.1%), with lower concentrations (0.01-0.1 microM) being ineffective. Conversely, in synaptosomes prepared from the dopamine-depleted striatum, NMDA maximally enhanced the K+/--evoked acetylcholine release at 0.1 microM (118 +/- 12.4%). Concentration-response curves of NMDA-evoked acetylcholine release in sham-operated rats could be superimposed on those observed in the contralateral striatum of the 6-hydroxydopamine-lesioned animals. The present data support the view of an increased glutamatergic regulation of striatal acetylcholine release via pre- and postsynaptic NMDA receptors during Parkinson's disease.

Acetylcholine↗

PubMed1999

Effects of cholecystokinin peptides and GV 150013, a selective cholecystokininB receptor antagonist, on electrically evoked endogenous GABA release from rat cortical slices.

The effects of cholecystokinin (CCK) agonists and antagonists on spontaneous and electrically evoked endogenous GABA release from rat cerebral cortex slices were evaluated. Neither the nonselective and CCK(B)-selective receptor agonists CCK-8S (3-1,000 nM) and CCK-4 (3-1,000 nM), respectively, nor the selective CCK(B) and CCK(A) receptor antagonists GV 150013 (3-30 nM) and L-364,718 (10-100 nM), respectively, significantly affected spontaneous GABA release. CCK-8S (1-1,000 nM) and CCK-4 (1-1,000 nM) increased the electrically (5 and 10 Hz)-evoked GABA release. On the contrary, GV 150013 (10 and 30 nM) significantly decreased the electrically evoked GABA release only when the slices were stimulated at the higher 10 Hz frequency. The CCK-8S- and CCK-4-induced increases in electrically evoked GABA release were counteracted by GV 150013, but not by L-364,718. Furthermore, GV 150013 at 3 nM shifted to the right the CCK-4 concentration-response curve, whereas at the higher 10 nM concentration it dramatically flattened the curve. Finally, in cortical slices obtained from rats chronically treated with GV 150013, the concentration-response curve of CCK-4 was shifted to the left and the peak effect of the peptide was significantly higher than that observed in naive animals. These results suggest that CCK increases electrically evoked, but not spontaneous, endogenous GABA release from rat cortical slices, possibly by activating local CCK(B) receptors. In addition, chronic treatment with the novel CCK(B) receptor antagonist GV 150013 leads to an enhanced responsiveness of cortical slices to CCK-4 application.

Adamantane↗

PubMed1999

L-glutamate and gamma-aminobutyric acid efflux from rat cerebrocortical synaptosomes: modulation by kappa- and mu- but not delta- and opioid receptor like-1 receptors.

The modulation by delta-, kappa-, mu-, and opioid receptor like-1 (ORL(1)) agonists and antagonists of L-glutamate (L-Glu) and gamma-aminobutyric acid (GABA) efflux from superfused rat cerebrocortical synaptosomes was studied. Tetrodotoxin (0.5 microM) inhibited the spontaneous efflux of both transmitters by 20%. Ca(2+) omission decreased GABA and facilitated L-Glu efflux. The neurotransmitter overflow evoked by K(+) concentrations in the 7.5- to 10-mM range was largely Ca(2+) dependent and tetrodotoxin sensitive. Neither the delta-receptor agonist deltorphin (up to 0.3 microM) nor the ORL(1) receptor agonist nociceptin (up to 1 microM) significantly affected either spontaneous or K(+)-evoked neurotransmitter efflux. Conversely, the ORL(1) ligand [Phe(1)(CH(2)-NH)Gly(2)]nociceptin(1-13)NH(2) (0.3 microM) caused a naloxone-sensitive inhibition of both L-Glu- and GABA-stimulated overflow. The kappa-receptor agonist (-)-U50,488 failed to modulate spontaneous L-Glu and GABA efflux. However, it similarly inhibited the K(+)-evoked overflow of both neurotransmitters (EC(50) approximately 100 nM; E(max) approximately 25-30% inhibition) in a norbinaltorphimine-sensitive manner. The selective mu-receptor agonist endomorphin 1 inhibited both spontaneous (EC(50) approximately 50 nM) and K(+)-evoked (EC(50) approximately 10 nM; E(max) approximately 50% inhibition) L-Glu efflux in a naloxone-sensitive manner. Conversely, it significantly inhibited only K(+)-evoked GABA efflux (EC(50) approximately 10 nM), although with a lower maximal effect (E(max) approximately 25-30% inhibition). It is concluded that, in the rat cerebral cortex, L-Glu and GABA efflux from nerve terminals is under the direct inhibitory control of kappa- and mu- (but not delta- or ORL(1)) receptors. Because glutamatergic terminals emerged as a preferential target of mu-receptor agonists, the activation of this receptor may advocate both relevant analgesic and neuroprotective effects.

Animals↗

PubMed1998

Protective effect of GV150526A on the glutamate-induced changes in basal and electrically-stimulated cytosolic Ca++ in primary cultured cerebral cortical cells.

Glutamate-induced changes in intracellular free Ca++ concentration ([Ca++]i) were recorded in resting and electrically-stimulated primary cultures of rat cerebral cortical cells, employing the Ca++ indicator Fura 2. A brief (10 min) exposure to glutamate led to a concentration-dependent basal [Ca++]i increase, measured 30 min after glutamate removal. In order to unmask more subtle modifications in [Ca++]i movements associated with neurosecretion, the glutamate effect was also studied in electrically-stimulated cells. The application of trains (10 s) of electrical pulses (intensity 30 mA, duration 1 ms) induced frequency-related Na+- and Ca++-dependent [Ca++]i transients. A 5 min treatment with 50 microM glutamate reduced to 48% the electrically-evoked [Ca++]i transients, evaluated 30 min after glutamate challenge. The neuroprotective effect of sodium 4,6-dichloro-3-[(E)-3-(N-phenyl)propenamide]indole-2-carboxylate (GV150526A), a new indole derivative with high affinity and selectivity for the glycine site of the NMDA receptor-channel complex, was compared with that of DL-2-amino-5-phosphonopentanoic acid (AP5), ifenprodil, 7-chlorokynurenic acid and 2,3-dihydroxy-6-nitro-7-sulfamoylbenzo(f)-quinoxaline (NBQX) on glutamate-induced [Ca++]i changes in resting and electrically-stimulated cells. In both experimental conditions, GV150526A showed to be the most potent compound. Moreover, GV150526A and 7-chlorokynurenic acid were 2-3 times more active in stimulated neurons than in resting neurons, indicating a major involvement of the glycine site in the protection of the cells kept in an active state.

Animals↗

PubMed1998

Reciprocal dopamine-glutamate modulation of release in the basal ganglia.

Dopaminergic and glutamatergic transmissions have long been known to interact at multiple levels in the basal ganglia to modulate motor and cognitive functions. One important aspect of their interactions is represented by the reciprocal modulation of release. This topic has been the object of interest since the late 70's, particularly in the striatum and in midbrain dopaminergic areas (substantia nigra and ventral tegmental area). Analysis of glutamate-dopamine interactions in the control of each other's release is complicated by the fact that both glutamate and dopamine act on multiple receptor subtypes which can exert different effects. Therefore, glutamatergic modulation of dopamine release has been reviewed by analyzing the effects of glutamatergic selective receptor agonists and antagonists in the striatum (both motor and limbic portions) and in midbrain dopaminergic areas, as revealed by in vitro (slices, cell cultures, synaptosomes) and in vivo (push-pull, microdialysis and voltammetry techniques) experimental approaches. The same approach has been followed for dopaminergic modulation of glutamate release. The facilitatory nature of glutamate modulating both presynaptic and dendritic dopamine release has clearly emerged from in vitro studies. However, evidence is presented that, at least in the striatum and in the nucleus accumbens of awake rats, glutamate-mediated inhibitory effects may also occur. In vitro and in vivo experiments in the striatum and midbrain dopaminergic areas mainly depict dopamine as an inhibitory modulator of glutamate release. However, in vivo studies reporting dopamine D1 receptor mediated facilitatory effects are also considered. Therefore, the general notion that glutamate and dopamine act oppositely to regulate each other's release, is only partly supported by the available data. Conversely, the nature of the interaction between the two neurotransmitters seems to vary depending on the experimental approach, the brain area considered and the subtype of receptor involved.

Animals↗

PubMed1998

Experimental protocol for studying delayed effects of in vitro ischemia on neurotransmitter release from brain slices.

The mechanisms by which ischemic injury leads to delayed neuronal death are not completely understood. Notably, no data are so far available on the modifications in neurosecretory responses evoked by a period of ischemia. Superfused brain slices represent a useful preparation in studying the effects of in vitro ischemia on neurotransmitter release. Using this experimental model we describe a protocol which allows to study not only the immediate effects of an ischemic insult, but also, more interestingly, its delayed (1 h) effects on the release of different neurotransmitters. A first pulse (S1) of 50 mM KCl was applied at the 60th min of perfusion and a second one was applied at the 210th min (S2). In vitro ischemia was performed from the 120th to the 150th min, during the inclusive period between the two depolarizing stimuli. The delayed effects of the ischemic treatment on slice response to KCl were calculated as S2/S1 ratio. This protocol allows to study neurotransmitter release mechanisms associated with postischemic neuronal death. Moreover it will be useful in the evaluation of the neuroprotective potential of new drugs.

Animals↗

PubMed1998

Pharmacological characterization of the nociceptin receptor mediating hyperalgesia in the mouse tail withdrawal assay.

1. The newly discovered neuropeptide nociceptin (NC) has recently been reported to be the endogenous ligand of the opioid-like orphan receptor. Despite its structural similarity to opioids, when injected intracerebroventricularly (i.c.v.) in the mouse, NC exerts a direct hyperalgesic effect and reverses opioid-induced analgesia. In the present investigation, these two effects of NC were evaluated under the same experimental conditions; in addition, a pharmacological characterization of the receptor mediating these central effects of NC was attempted. 2. NC caused a dose dependent (0.1-10 nmol/mouse), naloxone-insensitive reduction of tail withdrawal latency with a maximal effect of about 50% of the reaction time observed in saline injected mice. In the same range of doses, NC inhibited morphine (1 nmol/mouse) induced analgesia. 3. The effects of the natural peptide were mimicked by NCNH2 and NC(1-13)NH2 (all tested at 1 nmol/mouse) while 1 nmol NC(1-9)NH2 was found to be inactive either in reducing tail withdrawal latency or in preventing morphine analgesia. 4. [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 ([F/G]NC(1-13)NH2), which has been shown to antagonize NC effects in the mouse vas deferens, acted as an agonist, mimicking NC effects in both the experimental paradigms. In addition, when NC and [F/G]NC(1-13)NH2 were given together, their effects were additive. 5. These results demonstrate that both the direct hyperalgesic action and the anti-morphine effect of NC can be studied under the same experimental conditions in the mouse tail withdrawal assay. Moreover, the pharmacological characterization of the NC functional site responsible for these actions compared with the peripherally active site, indicates the existence of important differences between peripheral and central NC receptors.

Analgesia↗

PubMed1998

Different patterns of induction of FGF-2, FGF-1 and BDNF mRNAs during kindling epileptogenesis in the rat.

Neurotrophic factors (NTF) play important roles in the developing and in the adult brain. NTF involvement in neuronal plasticity is suggested by the modulation of NTF expression patterns in different physiological and pathological situations and by the effects they produce in the adult brain (e.g. axonal sprouting induction and neuroprotection). We used the RNAase protection assay to investigate the expression patterns of some NTFs during amygdala kindling, an animal model of epilepsy in which 'pathological' neuronal plasticity appears to occur. After a single kindling stimulation, fibroblast growth factor-2 (FGF-2) mRNA levels were increased in the hippocampus, the cortex and the hypothalamus, whereas they were not significantly altered in the thalamus and the striatum. A single stimulation did not alter fibroblast growth factor-1 (FGF-1) and brain-derived neurotrophic factor (BDNF) gene expression. Fully kindled animals, left unstimulated for a week, did not exhibit any alteration in the mRNA levels for any of the NTFs examined. However, in contrast with the effect of a single stimulation, amygdala stimulation of kindled animals (evoking a generalized tonic-clonic seizure) produced a great increase in hippocampal and cortical BDNF mRNA levels, but FGF-1 mRNA levels were not altered, and FGF-2 mRNA levels were significantly increased only in the cortex. These results suggest that different NTFs can be recruited at different stages of kindling epileptogenesis and, accordingly, may play different parts in the adaptive changes taking place in this experimental paradigm.

Amygdala↗

PubMed1998

Evidence for a striatal NMDA receptor modulation of nigral glutamate release. A dual probe microdialysis study in the awake freely moving rat.

Dual probe microdialysis was employed to characterize dialysate glutamate levels from the substantia nigra pars reticulata of awake freely moving rats, and to test its sensitivity to alterations in striatal neurotransmission including striatal N-methyl-D-aspartic acid (NMDA) receptor stimulation and blockade. Intranigral perfusion with low (0.1 mM) Ca2+ medium (60 min) did not affect nigral glutamate levels, whereas intranigral perfusion with tetrodotoxin (10 microM, 60 min) increased nigral glutamate levels. Perfusion of KCI (100 mM, 10 min) in the dorsolateral striatum transiently stimulated nigral glutamate levels (maximal increase + 60%), whereas intrastriatal perfusion (60 min) with low Ca2+ medium and tetrodotoxin gradually increased nigral glutamate levels. Intrastriatal perfusion with NMDA (0.1-100 microM, 10 min) dose-dependently stimulated glutamate levels in the substantia nigra pars reticulata. The NMDA (1 microM)-induced increase in nigral glutamate release was transient and maximal (+60% within 20 min), whereas that for NMDA (10 microM) had a slow onset but was long lasting (+35% after 60 min). Lower (0.1 microM) and higher (100 microM) NMDA concentrations were ineffective. The effect of intrastriatal NMDA (1 microM) was prevented by coperfusion with MK-801 (1 microM). Intrastriatal MK-801 (10 microM) alone gradually increased glutamate levels up to +50% after 60 min of perfusion. The present results suggest that glutamate levels in the substantia nigra pars reticulata are sensitive to changes in neuronal transmission in the dorsolateral striatum, and that striatal NMDA receptors regulate nigral glutamate release in both a tonic and phasic fashion.

Animals↗