Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Caerulein, cholecystokinin octapeptide (CCK-8) and diazepam delayed the onset of seizures produced by harman and thiosemicarbazide (TSC). Caerulein had the potency of diazepam, whereas CCK-8 was less active by a factor of four. The convulsions induced by isoniazid (INH) were very resistant to both caerulein and diazepam; CCK-8 was not tested against isoniazid. Haloperidol did not influence the effect of TSC; it enhanced isoniazid-induced seizures, and antagonized the convulsant effect of harman.
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PMID:Anticonvulsant effects of caerulein, cholecystokinin octapeptide (CCK-8) and diazepam against seizures produced in mice by harman, thiosemicarbazide and isoniazid. 626 41

Intraperitoneal administration of cholecystokinin octapeptide sulphate ester (CCK-8-SE) and nonsulphated cholecystokinin octapeptide (CCK-8-NS) enhanced the latency of seizures induced by picrotoxin in mice. Experiments with N- and C-terminal fragments revealed that the C-terminal tetrapeptide (CCK-5-8) was the active centre of the CCK octapeptide molecule. The analogues CCK-8-SE and CCK-8-NS (dose range 0.2-6.4 mumol/kg) and caerulein dose range 0.1-0.8 mumol/kg) showed bell-shaped dose-effect curves, with the greatest maximum inhibition for CCK-8-NS. The peptide CCK-5-8 had weak anticonvulsant activity in comparison to the octapeptides, 3.2 mumol/kg and larger doses of the reference drug, diazepam, totally prevented picrotoxin-induced seizures and mortality. The maximum effect of the peptides tested was less than that of diazepam. Experiments with analogues and derivatives of CCK-5-8 demonstrated that the effectiveness of the beta-alanyl derivatives of CCK-5-8 were enhanced and that they were equipotent with CCK-8-SE. Of the CCK-2-8 analogues, Ser(SO3H)7-Ac-CCK-2-8-SE and Thr(SO3H)7-Ac-CCK-2-8-SE and Hyp(SO3H)-Ac-CCK-2-8-SE were slightly more active than CCK-8-SE.
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PMID:Structure-activity and dose-effect relationships of the antagonism of picrotoxin-induced seizures by cholecystokinin, fragments and analogues of cholecystokinin in mice. 631 93

The effects of several doses of intracerebroventricularly injected cholecystokinin octapeptide sulfate ester (CCK-8-SE) and nonsulfated scholecystokinin octapeptide (CCK-8-NS) were studied on electroconvulsive shock (ECS)-induced retrograde amnesia, as measured in a one-trial step-through passive avoidance paradigm. Both CCK-8-SE and CCK-8-NS were able to attenuate amnesia slightly when they were injected into rats 10 min prior to ECS treatment, possibly by reducing the severity of the ECS-induced seizures. Of the treatments carried out immediately after ECS, only the 0.8 pmole dose of CCK-8-NS could significantly restore retrograde amnesia. After treatment 20 min prior to testing 24-hr retention, no effect of the peptides was observed. The lack of a dose-dependency and of any effect on retrieval raises the possibility that the CCK octapeptides influence memory processes by an indirect mechanism.
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PMID:The effects of sulfated and nonsulfated cholecystokinin octapeptides on electroconvulsive shock-induced retrograde amnesia after intracerebroventricular administration in rats. 632 92

Cholecystokinin-octapeptide (CCK-8S) is widely distributed in neurones of the central nervous system, where it is thought to act as a transmitter or modulator. CCK-8S has been shown to exert anti-convulsant activity in animal seizure models and changes in cortical and hippocampal CCK-immunoreactivity and preproCCK messenger RNA (mRNA) have been reported following electrically- and chemically-induced seizures. In the present study, the spatiotemporal effect of amygdaloid-kindled seizures on levels of preproCCK messenger RNA in rat brain were determined using quantitative in situ hybridization histochemistry. Stimulation-evoked seizures produced bilateral increases (45-70%) in preproCCK mRNA throughout layers II-III of the cerebral cortex. These increases were rapidly induced, occurring 30-60 min after the last stage 5 seizure, but transient, as no significant changes were detected after 2 h, or subsequently at 24 or 72 h, or 2-8 weeks, post-stimulation. Rapid changes in the relative levels of preproCCK mRNA, post-seizure, suggest a possible stabilization of preproCCK transcripts and increased production of CCK-8S peptide, which may be involved in anticonvulsant mechanisms in response to the acute seizures.
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PMID:Rapid but transient increases in cholecystokinin mRNA levels in cerebral cortex following amygdaloid-kindled seizures in the rat. 873 11

We studied the effects and the interactions of some candidate genes related to the pathogenesis of epilepsy using a domestic audiogenic epilepsy-prone rat, matched with the epilepsy-resistant Wistar rat, and primary fetal cerebral cortical neuronal cell cultures of both. The preliminary results showed that there was a possible abnormality of the CCK gene at the post-translational stage in the early postnatal period in P77PMC rat brain; the later rapidly increased rate of CCK-8 synthesis in the hippocampus and subcortical region may represent a compensatory response to the neuronal pathways involved in audiogenic seizures. CCK-8 can decrease the NMDA (1 microM)-induced free intracellular Ca2+ concentration, so it seems to be an inhibitory neuromodulator. In neuronal cell cultures, the NMDA (0.1 microM)-induced c-fos mRNA expression on culture day 18 in vitro was higher in P77PMC than Wistar rats (P < 0.05). Interleukin-1 (20 nM) can induce endogenous opioid mRNA expression and peptide release in neuronal cell cultures, which can be abolished by the addition of antisense oligos of c-fos/c-jun to cell cultures treated with interleukin-1. Both interleukin-1 and opioids can increase the free intracellular Ca2+ concentration, and their specific antagonists can reverse their effects, so they both seem to be excitatory neuromodulators in the CNS.
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PMID:Molecular neurobiological approach to the pathogenesis of epilepsy: a preliminary study. 888 76

Lasting changes in anxiety-like behavior (ALB) may be produced in several ways. These include partial limbic kindling, injection of the beta-carboline FG-7142, and brief, non-injurious, exposure of rodents to cats (predator stress). Both seizures and FG-7142 induce long-term potentiation (LTP) in efferent pathways of the amygdala known to participate in feline defensive behavior. By comparing the behavioral and physiological effects of partial kindling and injection of FG-7142, NMDA-dependent LTP in the right amygdalo-periacqueductal gray (PAG) pathway emerges as being critical to maintained increases in feline ALB. A similar dependence on NMDA-mediated processes is described for lasting increases in rodent ALB following predator stress. The lasting aftereffects of predator stress on a variety of measures parallel many of the symptoms of post-traumatic stress disorder (PTSD). Support is provided for the idea that behavioral changes following FG-7142 and predator stress may model anxiety associated with PTSD. Moreover, it is suggested that both models share mechanisms in common involving the PAG. These mechanisms likely involve initiation of LTP by NMDA receptors, and prolongation of LTP by CCKB receptors. To the extent that response to the stressors reviewed here mimics the symptoms of PTSD, the data implicate NMDA-mediated processes in the creation of what van der Kolk has called permanent emotional memories in PTSD. Their representation may be in the form of NMDA-dependent LTP of transmission within the amygdala and between the amygdala and its efferents. CCK may play a pivotal role in prolonging limbic LTP and anxiety following traumatic stress. Since block of CCKB receptors before and after the stressor prevents lasting increases in ALB, pharmacological intervention to block CCK receptors shortly after a traumatic stressor might be efficacious in mitigating the permanence of these emotional memories.
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PMID:Transmitter systems involved in neural plasticity underlying increased anxiety and defense--implications for understanding anxiety following traumatic stress. 941

Effects of the CCK(B) antagonists, CAM1028 and C1988, and the CCK(A) antagonist, CAM1481, were studied on the ethanol withdrawal syndrome. When handling-induced behavior was measured hourly for 12 h from withdrawal of ethanol, a small, but significant, protective effect was seen with 3 mg/kg CAM1028, but not with 0.3, 1, or 10 mg/kg. C1988 (0.3 1,3, or 10 mg/kg), or CAM1481 (0.1 or 1 mg/kg), had no effects. At 16 h from ethanol withdrawal, these ratings were significantly decreased by 3 mg/kg CAM1028 or C1988, but not by lower doses. At 16 h, CAM1481 had very small, but significant, protective effects. At 3 mg/kg, CAM1028, increased the latencies to audiogenic seizures, but had only small effects on convulsion incidence. CAM1481 did not alter the audiogenic convulsions. The decrease in convulsion thresholds to NMDLA, at 16 h from ethanol withdrawal, was completely prevented by CAM1028 or C1988, at 1 and at 3 mg/kg, but not by lower doses; CAM1481 had no significant effects. The results suggest change in CCK(B) receptors may be involved in the later stages of the ethanol withdrawal syndrome.
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PMID:CCK(B) antagonists protect against some aspects of the ethanol withdrawal syndrome. 958 57

Neuronal loss and irreversible brain damage often cause the worsening of symptoms and the decreased efficacy of pharmacological treatment occurring in epileptic patients and animal models of kindling. Recently we reported that the neurotransmitter/neuromodulatory peptide Cholecystokinin-8 (CCK-8) is able to induce the structural and functional neuronal recovery of chemical- and surgical-induced lesions when i.p. injected in rodents. The present study therefore, was aimed at verifying the hypothesis that treatment with a CCK-8 dose having a neuroprotective action might affect brain alterations and the development of kindling in adult rats receiving the convulsant agent pentylenetetrazole (PTZ). Compared to rats receiving Saline prior to PTZ, which manifested clonic-tonic seizures (Class 5 behavioural change scale) after three weeks of treatment, rats pre-treated with CCK-8 showed an improvement of behavioural score exhibiting myoclonus and occasionally tonic seizures (Class 3/4). This decreased susceptibility to develop convulsions was associated with the recovery of PTZ-induced reduction of ChAT levels in forebrain and GABA/GAD expression in the hippocampus. Furthermore, NPY immunoreactivity distribution and NPY mRNA levels were also increased in the hippocampus of rats receiving CCK-8 injection before each PTZ treatment. These data indicate that CCK-8 possesses the ability to prevent and/or suppress the convulsant effects of PTZ by stimulating the synthesis of neurotransmitters/peptides involved in the inhibition of hippocampal hyper-excitability. Our findings suggest that CCK-8 may have anticonvulsant and neuroprotective properties that merit further investigation.
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PMID:CCK-8 prevents the development of kindling and regulates the GABA and NPY expression in the hippocampus of pentylenetetrazole (PTZ)-treated adult rats. 1581 7

Major aspects of temporal lobe epilepsy (TLE) can be reproduced in mice following a unilateral injection of kainic acid into the dorsal hippocampus. This treatment induces a non-convulsive status epilepticus and acute lesion of CA1, CA3c and hilar neurons, followed by a latent phase with ongoing ipsilateral neuronal degeneration. Spontaneous focal seizures mark the onset of the chronic phase. In striking contrast, the ventral hippocampus and the contralateral side remain structurally unaffected and seizure-free. In this study, functional and neurochemical alterations of the contralateral side were studied to find candidate mechanisms underlying the lack of a mirror focus in this model of TLE. A quantitative analysis of simultaneous, bilateral EEG recordings revealed a significant decrease of theta oscillations ipsilaterally during the latent phase and bilaterally during the chronic phase. Furthermore, the synchronization of bilateral activity, which is very high in control, was strongly reduced already during the latent phase and the decrease was independent of recurrent seizures. Immunohistochemical analysis performed in the contralateral hippocampus of kainate-treated mice revealed reduced calbindin-labeling of CA1 pyramidal cells; down-regulation of CCK-8 and up-regulation of NPY-labeling in mossy fibers; and a redistribution of galanin immunoreactivity. These changes collectively might limit neuronal excitability in CA1 and dentate gyrus, as well as glutamate release from mossy fiber terminals. Although these functional and neurochemical alterations might not be causally related, they likely reflect long-ranging network alterations underlying the independent evolution of the two hippocampal formations during the development of an epileptic focus in this model of TLE.
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PMID:Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus. 1589 45

In our previous studies, we demonstrated that intraperitoneal (i.p.) injections with the neurotransmitter/neuromodulatory peptide Cholecystokinin-8 (CCK-8) stimulate the synthesis of the neurotrophin nerve growth factor (NGF) resulting in the structural and functional recovery of neuronal damage. This neurotrophin-mediated neuroprotective action of CCK-8 has opened a new perspective for a better understanding of the CCK neurobiological and pharmacological properties. To explore the possible beneficial effects of the CCK-induced increase of neurotrophin availability in brain, we compared the effects of i.p. CCK-8 in healthy rats and in a chemical kindling model using a subconvulsive dose of pentylenetetrazol (PTZ). Behavioural changes were monitored during treatment and classified according to a six-point scale. After 3 weeks of treatment (12 trials), the PTZ group of rats manifested generalized clonic-tonic seizures (Class 5 behaviour). For this reason, this time point was chosen to compare the effects of CCK-8 treatment on the expression of NGF, the brain derived neurotrophin factor (BDNF) and their receptors in the septum and hippocampus. We found that repeated i.p. injections with CCK-8 in adult rats result in: (1) an increase of NGF and BDNF protein and mRNA levels in the septum and hippocampus; (2) a down-regulation of TrkA and p75NTR and an up-regulation of TrkB; (3) reduced susceptibility to develop chemical kindling; (4) recovery of the PTZ-induced changes in the expression of neurotrophin receptors in the septal and hippocampal tissues. This data clearly indicates that CCK-induced variation of neurotrophin synthesis in brain is able to influence the susceptibility to develop seizures in adult rats most probably by counteracting the progressive neuronal dysfunction and/or damage.
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PMID:CCK-8 induces NGF and BDNF synthesis and modulates TrkA and TrkB expression in the rat hippocampus and septum: Effects on kindling development. 1696 63


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