Functional activation of somatostatin and neuropeptide Y containing neurons in experimental models of limbic seizures.
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Animals↗
Biomedical subjects
A Vezzani
Publications and source records attributed to A Vezzani.
Alternative splicing at the C-terminal but not at the N-terminal domain of the NMDA receptor NR1 is altered in the kindled hippocampus.
Several lines of evidence suggest that N-methyl-D-aspartate (NMDA) receptors significantly contribute to the development of kindling. In addition, a lasting enhancement of the NMDA receptor function has been suggested to play a significant role in the chronic hyperexcitability occurring in the hippocampus after kindling epileptogenesis. We have investigated whether hippocampal kindling induces changes in the NMDA receptor at the molecular level by assessing the expression of mRNAs of the different spliced variants at the N-terminal (exon 5) and C-terminal (exon 21) position of the NMDA receptor 1 (NR1) gene by means of the reverse transcription-polymerase chain reaction. Alternative splicing at exon 5 confers different sensitivity of the NMDA receptor to polyamines while exon 21 encodes a 37-amino acid insert containing the major phosphorylation sites for protein kinase C. One week after the acquisition of stage 5 of kindling in rats (generalized tonic-clonic seizures), the relative abundance of the two alternatively spliced forms at the C-terminal domain, respectively containing (+) or lacking (-) exon 21, was reversed compared to controls (implanted with electrodes but not stimulated) in the dorsal hippocampus ipsilateral and contralateral to the electrical stimulation. The exon 21+/exon 21- mRNA ratio for controls was 1.3 +/- 0.04 (mean +/- SE); for ipsilaterally kindled rats it was 0.64 +/- 0.05 (P < 0.05), and for contralaterally kindled rats it was 0.48 +/- 0.07 (P < 0.01). Similar bilateral effects were observed in the ventral hippocampus (temporal pole). No changes were found 4 weeks after stage 5 seizures and 1 week after the induction of a single afterdischarge. No significant alterations were induced by kindling in the relative abundance of the spliced variants containing or lacking exon 5. Our findings show selective changes in alternative splicing of the NR1 gene after repeated application of an epileptogenic stimulus. This may generate receptors with different functional properties, which may contribute to the increased sensitivity for the induction of generalized seizures during kindling.
Alternative Splicing↗
Electrical kindling is associated with a lasting increase in the extracellular levels of kynurenic acid in the rat hippocampus.
Endogenous kynurenic acid (KYNA), an excitatory amino acid receptor antagonist with antineurotoxic and anticonvulsant activity, was assessed by microdialysis in the hippocampus of kindled rats. One week after the completion of amygdala or hippocampal kindling (stage 5), the dialysate concentration of KYNA in the hippocampus of both hemispheres was 1.7 +/- 0.1-fold higher than in shams (P < 0.01). Veratridine (50 microM), applied through the probe, reduced extracellular KYNA by 28% within 1 h in controls (P < 0.05), but was ineffective in stage 5 kindled rats. At the preconvulsive stage 2, dialysate KYNA concentration and the effect of veratridine were similar to controls. The activity of KYNA's biosynthetic enzyme, kynurenine aminotransferase, did not change in the hippocampus 1 week after stage 5 seizures. These data indicate an enhanced liberation of KYNA in teh hippocampus of fully kindled animals due to an impairment of normal regulatory mechanisms. This may be of relevance for the control of hippocampal excitability during epileptogenesis.
Animals↗
Extracellular glutamate levels in the hypothalamus and hippocampus of rats after acute or chronic oral intake of monosodium glutamate.
Using brain microdialysis we studied the effect of high doses of monosodium glutamate (MSG) on the extracellular concentration of glutamate in the hypothalamus and in the hippocampus of freely moving rats. MSG at 4 g/kg (40% solution) given by gavage caused a significant increase in plasma (5.3 +/- 0.4-fold, P < 0.01) and extracellular glutamate in the hippocampus (4.2 +/- 0.6-fold, P < 0.01) and in the hypothalamus (8.9 +/- 1.7-fold, P < 0.01) compared to control rats receiving a 40% sucrose solution (10 ml/kg). The peak increase was found within 40 min after MSG administration then declining to baseline in the next 80 min. No changes were found in glutamate tissue concentrations. Twenty-one days after ad libitum MSG intake with the diet (approximately 4 g/kg) no changes were found, in plasma, in extracellular and tissue concentration of glutamate in the hypothalamus compared to rats fed with a normal diet. Glutamate release induced by 200 mM KCl was not modified as well. Histological analysis of Nissl-stained brain tissue slices did not reveal any obvious cell loss in the hippocampus after acute or chronic MSG administration.
Administration, Oral↗
Trans-synaptic modulation of striatal ACh release in vivo by the parafascicular thalamic nucleus.
Electrical stimulation of the parafascicular but not the ventrolateral or dorsomedial thalamic nucleus (ten 0.5 ms, 10 V pulses, 140 microA) of freely moving rats induced a frequency-dependent (2.5, 5, 10 and 20 Hz) increase in the extracellular acetylcholine (ACh) content of the dorsal striatum, assessed by trans-striatal microdialysis. The time-dependent effect of 10 Hz stimulation was studied. The peak increase, 39% above baseline, was attained during 4 min of stimulation. This was blocked by coperfusion with 5 microM tetrodotoxin, indicating that the release we measured represents a physiological process. The facilitatory effect of parafascicular nucleus stimulation does not appear to be associated with indirect action through the cerebral frontal cortex because acute lesion of the excitatory corticostriatal afferents, which by itself reduced basal ACh release by 40%, did not modify the effect of 10 Hz stimulation. The possible involvement of the fasciculus retroflexus in the facilitation of ACh release was also ruled out. The non-competitive NMDA-type receptor antagonist MK-801, applied by reversed dialysis (30 microM) or systemically injected (0.2 mg/kg), significantly reduced the basal ACh output and prevented the tetanus-evoked increase in ACh release. The results provide in vivo evidence that the activity of the cholinergic neurons in the dorsal striatum is trans-synaptically modulated by parafascicular nucleus excitatory afferents through activation of the NMDA subtype of glutamate receptors that is probably located in the striatum.
Acetylcholine↗
Functional effects of D-Phe-c[Cys-Tyr-D-Trp-Lys-Val-Cys]-Trp-NH2 and differential changes in somatostatin receptor messenger RNAs, binding sites and somatostatin release in kainic acid-treated rats.
In situ hybridization histochemistry for somatostatin receptors-1, -2, -3 and -4 section and receptor autoradiography using [125I]CGP 23996, [125I]somatostatin-28, [125I]seglitide and [125I]Tyr3 octreotide were carried out to determine the expression of somatostatin receptor messenger RNAs and binding sites in the hippocampus and cerebral cortex of rats 21 days following generalized limbic seizures induced by subcutaneous injection of 12mg/kg kainic acid. In control rats, somatostatin-1 to somatostatin-4 receptor messenger RNAs were found in the pyramidal layer and granule cell layer of the dentate gyrus. After kainate treatment, the CA1 subfield displayed a selective decrease in somatostatin-3 and somatostatin-4 receptor hybridization signals of 35 and 41%, respectively, whereas no changes were observed in the remaining hippocampal areas. Somatostatin-1 and somatostatin-2 receptor messenger RNA expression in the hippocampus remained unaffected by kainate treatment. No effect of kainate was observed in the expression of somatostatin receptor messenger RNAs in the cerebral cortex. In control rats, the selective somatostatin-2 receptor ligands, [125I]seglitide and [125I]Tyr3 octreotide and the non-selective somatostatin receptor ligands [125I]CGP 23996 and [125I]somatostatin-28, labelled preferentially the stratum oriens and radiatum CA1, the granule and molecular layers of the dentate gyrus and the deep layers of the cerebral cortex. [125I]somatostatin-28 and [125I]CGP 23996 labelled sites were selectively decreased by 32 and 39%, respectively, in the stratum radiatum CA1 after kainate treatment. [125I]CGP 23996 binding was also decreased by 35% in the stratum oriens CA1 and by 36% on average in the stratum oriens and radiatum CA3. [125I]seglitide and [125I]Tyr3 octreotide binding was not affected by kainate in any hippocampal region. The granule and molecular layers of the hippocampus and the layers IV-VI of the cerebral cortex did not show changes in binding sites for any of the radioligands analysed. A 18 and 35% decrease in the spontaneous and 50 mM KCl-induced somatostatin release from hippocampal slices was found two days after kainate, a likely reflection of neuronal cell loss. No differences in somatostatin release were observed 21 days after kainate treatment. At this latter time, the rats had an enhanced susceptibility to tonic-clonic seizures induced by intraperitoneal injection of 30 mg/kg pentylenetetrazol, a subconvulsant dose in naive rats. Bilateral infusion of 6 micrograms RC 160, a selective somatostatin-2 receptor agonist, in the dentate gyrus 21 days after kainate, significantly reduced (P < 0.05) the number of animals with tonic-clonic seizures induced by pentylenetetrazol.(ABSTRACT TRUNCATED AT 400 WORDS)
Amino Acid Sequence↗
Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy.
Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus). After rapid kindling, somatostatin immunoreactivity was strongly increased in interneurons and in the outer and middle molecular layer of the dentate gyrus. In four of six post-status epilepticus rats (status epilepticus I rats), somatostatin immunoreactivity was slightly increased in the dorsal but decreased in the ventral dentate gyrus and molecular layer. Somatostatin immunoreactivity decreased in neurons of the dorsal hilus in the two other post-status epilepticus rats investigated, while a complete loss was found in the respective ventral extension (status epilepticus-II rats). These changes were associated with a different extent of neurodegeneration as assessed by Nissl staining. Similarly, neuropeptide Y immunoreactivity was enhanced in neurons of the hilus and in the middle and outer molecular layer of the dentate gyrus in the dorsal hippocampus of rapidly kindled and status epilepticus-I rats. Neuropeptide Y and neurokinin B immunoreactivity was enhanced in the mossy fibers of all post-status epilepticus rats, but not in the rapidly kindled rats. In status epilepticus-II rats, neuropeptide Y-and neurokinin B-positive fibers were also detected in the infrapyramidal region of the stratum oriens of CA3 and in the inner molecular layer of the dentate gyrus in the dorsal and ventral hippocampus respectively, labeling presumably sprouted mossy fibers. Increased staining of neuropeptide Y and neurokinin B was found in the alveus after rapid kindling. Cholecystokinin immunoreactivity was markedly increased in the cerebral cortex, Ammon's horn and the molecular layer of the dentate gyrus in the ventral hippocampus of rapidly kindled and post-status epilepticus rats. The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons. These changes may be involved in chronic epileptogenesis, which evolves in response to limbic seizures.
Animals↗
Adaptive changes in the NMDA receptor complex in rat hippocampus after chronic treatment with CGP 39551.
Chronic treatment of adult rats with DL-(E)-2-amino-4-methyl-5-phosphono-3-pentenoic carboxyethylester (CGP 39551) (30 mg/kg orally for 12 days) induced a significant increase, 72 h after the last dose, in the N-methyl-D-aspartate (NMDA)-sensitive [3H]glutamate binding in the hippocampal pyramidal layer (stratum oriens CA1, CA3: +51% on average; stratum radiatum CA1, CA3: +40% on average; stratum pyramidale CA1: +20%, CA3: +55%) and in the dentate gyrus (+43%) compared to vehicle-injected animals, as assessed by quantitative receptor autoradiography. Similar results were obtained using the NMDA receptor antagonist, [3H]DL-(E)-2-amino-4-propyl-5-phosphono-3-pentenoic acid (CGP 39653). Saturation experiments showed that the increase in [3H]CGP 39653 binding was due to the maximum number of receptors, without changes in affinity. The same regimen did not alter [3H]N-(1-[2-thienyl]-cyclohexyl)-3,4-piperidine (TCP) binding to the ion channel coupled to the receptor but prevented D-serine (5 microM)-induced enhancement of [3H]glutamate binding. NMDA (3-300 microM) enhanced [3H]noradrenaline release from hippocampal slices, and 7-Cl-kynurenic acid (5-100 microM) and (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclo-hepten-5,10-imine maleate (MK 801) (0.03-0.3 microM), antagonists at the glycine site and ion channel respectively, antagonized this effect to the same extent in CGP 39551-treated rats and controls. Chronic CGP 39551 did not affect the neurotoxic potency of quinolinic acid, a selective agonist at the NMDA receptor, injected in the hippocampus.(ABSTRACT TRUNCATED AT 250 WORDS)
2-Amino-5-phosphonovalerate↗
Enhanced neuropeptide Y release in the hippocampus is associated with chronic seizure susceptibility in kainic acid treated rats.
We measured the release of neuropeptide Y (NPY) from hippocampal slices of rats at various times after limbic seizures induced by a subcutaneous injection of 12 mg/kg kainic acid (KA). Two days after KA, 100 mM KCl induced a 1.6 +/- 0.2-fold increase in NPY release compared to saline-injected rats (P < 0.05), while spontaneous and 50 mM KCl-induced release were unchanged. Thirty days after KA, the spontaneous and 100 mM KCl-induced efflux of NPY was enhanced 2-fold on average (P < 0.01) compared to controls, while no significant differences were found using 50 mM KCl. Tissue concentration of NPY was raised 2.2 +/- 0.2 times (P < 0.01) 30 days after KA. Thirty days after KA, the rats showed enhanced susceptibility to tonic-clonic seizures, assessed using a normally subconvulsive dose of pentylenetetrazol (PTZ; 30 mg/kg). A selective antibody (Ab) raised against NPY in a rabbit was infused bilaterally for three days in the CA3 area and dentate gyrus (DG) of the dorsal hippocampus of rats treated 30 days before with KA. This significantly reduced (P < 0.05) the number of animals with tonic-clonic seizures induced by 30 mg/kg PTZ, compared to KA treated rats which received the inactivated Ab. The Ab was ineffective in naive rats injected with a full convulsive dose of PTZ (55 mg/kg). The present results show that neuronal release of NPY is enhanced in the hippocampus after limbic seizures induced in rats by KA. This effect persists for at least 30 days and may contribute to the chronically enhanced susceptibility to seizures after injection of this toxin.
Animals↗
Impulse flow dependency of galanin release in vivo in the rat ventral hippocampus.
Using microdialysis and a sensitive RIA, we have studied the in vivo release of the neuropeptide galanin (GAL) from the ventral hippocampus of freely moving rats. The spontaneous outflow of GAL-like immunoreactivity (GAL-LI) (1.8 +/- 0.3 fmol per ml per 20 min) was dependent on the presence of extracellular Ca2+ and was inhibited by tetrodotoxin. Evoked release induced by infusion of KCl (60 mM) or veratridine (148 microM) was also Ca(2+)-dependent and sensitive to tetrodotoxin. Electrical stimulation of the ventral limb of the diagonal band nuclei induced a frequency-dependent (50-200 Hz) and tetrodotoxin-sensitive overflow of GAL-LI in the hippocampus. In vitro GAL-LI release (1.0 +/- 0.02 fmol per ml per 5 min), studied in slices of rat ventral hippocampus, was also Ca(2+)-dependent and was increased in a concentration-dependent manner by KCl depolarization. This study demonstrates the release of the neuropeptide GAL in the rat central nervous system. The in vivo release is related to the activity of the cholinergic GAL-LI-containing cells in the septal diagonal band nuclei. The results are discussed in relation to the coexistence of GAL and acetylcholine within the septal/diagonal band complex.
Animals↗
Changes in the ADP-ribosylation status of some hippocampal proteins are linked to kindling progression.
The N-methyl-D-aspartate (NMDA) receptors are a class of excitatory amino acid receptors in the brain which are important for the induction of kindling and kindling-like phenomena. Post hoc sodium nitroprusside-induced ADP ribosylation of some proteins (particularly a p43 and a p39 protein) in homogenates from stimulated hippocampus was reduced at preconvulsive stage II and stage V (tonic-clonic seizures) of dentate gyrus kindling compared with controls. This effect, which probably reflects enhanced endogenous ADP ribosylation, depends on the progressive activation of the NMDA receptors and on the generation of nitric oxide (NO). The early occurrence and the persistence of these modifications suggest they may be associated to the long-lasting changes in neuronal function induced by kindling.
2-Amino-5-phosphonovalerate↗
Electrical kindling of the hippocampus is associated with functional activation of neuropeptide Y-containing neurons.
The release of neuropeptide Y (NPY) was measured from hippocampal slices of rats at stage 2 (preconvulsive stage) and stage 5 (full seizure expression) of electrical kindling of the dorsal hippocampus (upper blade of the dentate gyrus). Spontaneous release in naive rats (9.0 +/- 0.8 fmol/ml every 10 min) was independent of external Ca2+ but was reduced by 38 +/- 3.6% (P < 0.05) during 20 min incubation with 5 microM tetrodotoxin. Spontaneous efflux in naive rats did not differ from that in shams (implanted with electrodes but not stimulated) or in rats kindled to stage 2 and stage 5. Twenty-five, 50 and 100 mM KCl induced a concentration-dependent release of NPY (P < 0.05 and P < 0.01 at 25 and 50-100 mM respectively) from slices of shams. The effect of 100 mM KCl was reduced by 94 +/- 1% (P < 0.01) in the absence of Ca2+. Two days after the last stage 2 stimulation and 1 week after the last stage 5 seizure, NPY release was significantly larger than in shams at all KCl concentrations in the stimulated and contralateral hippocampus (P < 0.05 and P < 0.01). Forty-eight hours after one single after-discharge and 1 month after the last stage 5 seizure, 50 mM KCl induced a significantly larger release of NPY in the stimulated and contralateral hippocampus (P < 0.01 and P < 0.05), although the effect was less than during kindling.(ABSTRACT TRUNCATED AT 250 WORDS)
Analysis of Variance↗
Increased expression of GAP-43, somatostatin and neuropeptide Y mRNA in the hippocampus during development of hippocampal kindling in rats.
The expression and distribution of the mRNA coding for the growth-associated protein-43 (GAP-43), a putative marker for neuritic growth, for preprosomatostatin and the preproneuropeptide Y (ppNPY) were analysed in the rat hippocampus during the development of hippocampal kindling by an in situ hybridization technique and computer-assisted grain counting in the cell. The levels of GAP-43 mRNA increased significantly in the CA3 pyramidal neurons and hilar polymorphic neurons of the dentate gyrus 2 days after stage 2 of kindling (preconvulsive stage) but not stage 5 (full seizure expression) in the stimulated hippocampus. The distribution of GAP-43 mRNA was the same in the hippocampus of kindled rats as in sham-stimulated animals. Preprosomatostatin mRNA and ppNPY mRNA contents rose significantly in the hilar polymorphic neurons of the dentate gyrus of the stimulated and contralateral hippocampus at both stages of kindling, with the greatest effect at stage 5. In addition, the number of ppNPY mRNA neurons in the fascia dentata was significantly higher in kindled rats than in controls, but there were no differences in the number of preprosomatostatin mRNA-positive cells. Preprosomatostatin and ppNPY mRNAs were also increased in the neurons of the stratum oriens of the CA1-CA3 subfield of fully kindled animals, whereas at stage 2 only neurons of the CA1 stratum oriens showed a significant increase of preprosomatostatin mRNA. No changes in preprosomatostatin and ppNPY mRNA expression were observed in the various regions of the hippocampus after a single afterdischarge or 1 month after stage 5.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Anti-somatostatin antibody enhances the rate of hippocampal kindling in rats.
A somatostatin-specific antibody (Ab) (1:250) was continuously infused into the stimulated dorsal hippocampus of rats from 4 days before to 26 days after the beginning of kindling or until the first stage 5. Controls received boiled Ab. The number of stimulations to the first stage 5 were reduced by 41 +/- 4% (P < 0.01, Student's t-test) in animals infused with the Ab compared to controls. The cumulative after-discharge in the stimulated hippocampus was slightly, although not significantly, reduced. Kindling was not affected when the Ab was infused only during the first 10 stimulations (stage 2). Histological analysis showed no neurotoxic effects in the hippocampus as a consequence of Ab infusion.
Animals↗
Extracellular somatostatin measured by microdialysis in the hippocampus of freely moving rats: evidence for neuronal release.
Intracerebral microdialysis combined with a sensitive and specific radioimmunoassay was used to monitor the neuronal release of somatostatin (somatostatin-like immunoreactivity, SLI) in the dorsal hippocampus of freely moving rats. The sensitivity of the radioimmunoassay was optimized to detect < 1 fmol/ml. The basal concentration of SLI in 20-min dialysate fractions (5 microliters/min) collected 24 h after probe implantation was stable over at least 200 min. The spontaneous efflux dropped by 54 +/- 6.4% (p < 0.05) when Ca2+ was omitted and 1 mM EGTA added to the Krebs-Ringer solution and by 65.5 +/- 3.2% (p < 0.05) in the presence of 1 microM tetrodotoxin. Depolarizing concentrations of the Na+ channel opener veratridine (6.25, 25, 100 microM) induced 11 +/- 2 (p < 0.05), 17 +/- 2 (p < 0.05), and 21 +/- 5 (p < 0.01) fold increase in SLI concentration, respectively, during the first 20 min of perfusion. The effect of 100 microM veratridine was blocked by coperfusion with 5 microM tetrodotoxin (p < 0.01) and reduced by 79% (p < 0.01) in the virtual absence of Ca2+. Neuronal depolarization by 20 min of perfusion with Krebs-Ringer solution containing 25 and 50 mM KCl and proportionally lowered Na+ increased the dialysate SLI 4.4 +/- 1 (p < 0.05) and 17 +/- 3 (p < 0.01) fold baseline, respectively. Ten micromolar ouabain, a blocker of Na+,K(+)-ATPase, increased the dialysate SLI 15-fold baseline, on average (p < 0.05), during 80 min of perfusion. The results demonstrate the suitability of brain microdialysis for monitoring the neuronal release of SLI and for studying its role in synaptic transmission.
Animals↗
Chronic infusion of quinolinic acid in rat striatum: effects on discrete neuronal populations.
The intrastriatal infusion of relatively low doses of quinolinic acid (Quin, 4-10 nmol/h) for 1 or 2 weeks induced time-dependent degeneration of neuronal cells. We examined the effects of these infusions on discrete cellular populations. The distribution of somatostatin (SOM)-positive neurons labelled by immunocytochemistry or by NADPH-diaphorase histochemistry and of cholinergic cells stained by acetylcholinesterase was quantified in the peripheral portion of the lesioned area. SOM-positive cells did not appear selectively spared by Quin infusion. The proportion of SOM- and NADPH-diaphorase-positive neurons killed by exposure to Quin was similar to or higher than the percentage of total neurons degenerated (from 30 to 85%). A selective sparing of cholinergic cells was observed in all conditions examined; perfusion of 6 nmol/h for a week induced 65% of cell death while not more than 30% of cholinergic neurons were killed. Thus, the neurochemical similarity between the degenerative effects of intrastriatal Quin and Huntington's disease (HD) did not appear confirmed by the chronic perfusion of low doses of Quin for SOM-positive neurons, whereas an analogy between Quin's effects and HD was suggested by the pattern of AChE staining.
Acetylcholinesterase↗
Somatostatin release is enhanced in the hippocampus of partially and fully kindled rats.
The release of somatostatin (somatostatin-like immunoreactivity) from hippocampal slices during the development of hippocampal kindling in rats was measured under resting and depolarizing conditions. Preliminary experiments in naive rats showed that the spontaneous efflux of somatostatin (4.0 +/- 0.3 fmol/ml every 10 min) was independent of external Ca2+ but was reduced to 71.5 +/- 6% of baseline (P < 0.05) during 20 min incubation with 5 microM tetrodotoxin. Neuronal depolarization with 25, 50 and 100 mM KCl induced a Ca(2+)-dependent somatostatin release, respectively 4.3 +/- 0.4, 16.7 +/- 1.6 and 22.0 +/- 1.3 times baseline (P < 0.01). Veratridine caused a dose-dependent Ca2+ and tetrodotoxin (5 microM) sensitive release ranging from 6.5 +/- 0.1 to 13.0 +/- 1.4 times baseline at 1.4 microM and 50 microM respectively (P < 0.01). One week after the last of three consecutive stage 5 seizures (full seizure expression) or 48 h after the last stage 2 stimulation (preconvulsive stage), 50 mM KCl-induced somatostatin release was significantly higher (1.8 +/- 0.1, P < 0.01) than in shams (animals implanted with electrodes but not stimulated) in the stimulated and contralateral hippocampus. Somatostatin release measured under resting conditions was increased by 1.5 times in the stimulated hippocampus at stage 2 (P < 0.05) and by 2.2 and 1.7 times in both hippocampi at stage 5 (P < 0.01). Forty-eight hours after the induction of a single afterdischarge no significant changes were found in either spontaneous or 50 mM KCl-induced release of somatostatin.(ABSTRACT TRUNCATED AT 250 WORDS)
Animals↗
Biochemical and functional studies on noradrenergic and peptidergic neurotransmission in hippocampal kindling.
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Animals↗