Effect of CCK-8 on audiogenic epileptic seizure in P77PMC rats

doi:10.1016/0143-4179(93)90072-I

Neuropeptides

Volume 25, Issue 1, July 1993, Pages 73-76

https://doi.org/10.1016/0143-4179(93)90072-I Get rights and content

Abstract

P77PMC rat is a breed of rat with congenital audiogenic seizure(AS). AS attacks were suppressed by cholecystokinin octapeptide (CCK-8) injected intraperitoneally (i.p.) at a dose of 50 μg/kg, but not at 25 μg/kg. Radioimmunoassay study showed that the CCK-8 immunoreactivity (IR) in the cerebrocortex and hippocampus is much lower in P77PMC rats than that of Wistar rats. The results suggest that a low cerebral content of CCK-8 may account for the high susceptibility of audiogenic seizure in P77PMC rats.

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Cited by (18)

A prospective study on changes in blood levels of cholecystokinin-8 and leptin in patients with refractory epilepsy treated with the ketogenic diet
2016, Epilepsy Research
Citation Excerpt :
The anticonvulsive action of CCK has also been proven in various animal studies. Intracerebroventricular administration of CCK-8 in rats and intraperitoneal administration in mice and rats diminished seizures induced by different provoking mechanisms in epilepsy models (Kadar et al., 1987, 1984, 1983; Zhang et al., 1993). CCK-8 also amplified the anti-convulsive effect of the AED vigabatrine in a rat model for human partial epilepsy (Ferraro and Sardo, 2009).
To evaluate the changes in serum CCK-8 and leptin levels in patients with refractory epilepsy treated with the ketogenic diet (KD).
In this prospective study, patients aged between one and 40 years with refractory epilepsy were included. CCK-8 and leptin were measured in serum at baseline and after three and 12 months of treatment with the KD using an enzyme-linked Immunoabsorbant Assay. Seizure frequency and responsiveness were calculated.
Fifty-four patients were included; 26 patients (48%) were still on the KD at 12 months. After three and 12 months, respectively, 39% and 26% were responders. CCK-8 values were statistically significantly increased at three months (p = 0.005) and 12 months (p = 0.012). In responders, at three months follow-up, this increase of CCK-8 was significant (p = 0.020), whereas in the non-responders it was not (p = 0.34). Leptin values were decreased at three and 12 months, the decrease at three months being statistically significant in post-pubertal men (p = 0.028) and post-pubertal women (p = 0.007).
In responders to the KD, serum CCK-8 increased statistically significantly during treatment at three months. Serum leptin decreased statistically significantly at three months in men and in post-pubertal women. It is plausible that the increase of CCK-8 and the decrease of leptin contribute to the anti-convulsive effect of the KD.
Role of cholecystokinin type B receptors in ultrasound induced behavior in rats
1999, Peptides
The cholecystokinin-tetrapeptide (CCK-4) can induce panic attacks in humans. The present study investigates the effects of CCK-4 and the CCK-B receptor antagonist l-365.260 on ultrasound induced defense behavior in the rat that may model the unconditioned aspects of panic behavior in man. CCK-4 (50 μg/kg) increased the defense response induced by ultrasound (95 dB) an effect prevented by pretreatment with l-365.260 (10 μg/kg). Compared with other antipanic/panicogenic drugs the effects of CCK-4 and l-365.260 were relatively small. In conclusion, drugs acting at the CCK-B receptor appear to have only a minor role in the modulation of an unconditioned aversive response.
Expression of cholecystokinin messenger RNA in reciprocally-connected auditory thalamus and cortex in the rat
1997, Neuroscience
Cholecystokinin exerts a potent antiepileptic action in mammalian auditory system and undergoes seizure-mediated up-regulation. The present study investigated cholecystokinin messenger RNA expression in the reciprocally-connected auditory thalamus and cortex in the rat. Immunofluorescence in situ hybridization was performed using a 24-base cholecystokinin-messenger RNA oligonucleotide probe. Corticothalamic projection neurons were identified by means of the retrograde fluorescent tracer rhodamine latex microspheres injected into the medial geniculate body. In our experiments, cholecystokinin messenger RNA transcripts were found in about 80% of neurons located within the reciprocally-connected regions of the medial geniculate body and the auditory cortices.
These observations provide evidence of cholecystokinin production in the reciprocally-connected regions of the auditory thalamus and cortex, the structures which jointly create the thalamo-cortico-thalamic circuit which has been implicated in seizure genesis.
Rats with decreased brain cholecystokinin levels show increased responsiveness to peripheral electrical stimulation-induced analgesia
1997, Brain Research
Using the P77PMC strain of rat, which is genetically prone to audiogenic seizures, and also has decreased levels of cholecystokinin (CCK), we examined the analgesic response to peripheral electrical stimulation, which is, in part, opiate-mediated. A number of studies have suggested that CCK may function as an antagonist to endogenous opiate effects. Therefore, we hypothesized that the P77PMC animals would show an enhanced analgesic response based on their decreased CCK levels producing a diminished endogenous opiate antagonism. We found that the analgesic effect on tail flick latency produced by 100 Hz peripheral electrical stimulation was more potent and longer lasting in P77PMC rats than in control rats. Moreover, the potency of the stimulation-produced analgesia correlated with the vulnerability to audiogenic seizures in these rats. We were able to block the peripheral electrical stimulation-induced analgesia (PSIA) using a cholecystokinin octapeptide (CCK-8) administered parenterally. Radioimmunoassay showed that the content of CCK-8 in cerebral cortex, hippocampus and periaqueductal gray was much lower in P77PMC rat than in controls. These results suggest that low CCK-8 content in the central nervous system of the P77PMC rats may be related to the high analgesic response to peripheral electrical stimulation, and further support the notion that CCK may be an endogenous opiate antagonist.
Lipofectin-facilitated transfer of cholecystokinin gene corrects behavioral abnormalities of rats with audiogenic seizures
1997, Neuroscience
To evaluate the potential for lipofectin-mediated central nervous system gene transfer, the plasmid coding for cholecystokinin was administered intracerebroventricularly to rats, which have congenital audiogenic seizures and high responses to peripheral electric stimulation-induced analgesia. Previous studies had shown that low brain cholecystokinin levels may be the neurochemical variable of rat's audiogenic seizure and high responses to the analgesia because cholecystokinin is an anticonvulsant and anti-opioid neuropeptide. Gene transfer of cholecystokinin corrected the increased susceptibility to audiogenic seizures and the high responses to analgesia for about one week. Similar administration of plasmid expressing β-galactosidase indicated that the vector mainly transfected ependymal cells lining the ventricle and pia mater cells. The increased cholecystokinin messenger RNA and immunoreactivity in the hippocampus following stereotactic intrahippocampal administration of cholecystokinin plasmid was also demonstrated with in situ hybridization and immunohistochemistry techniques.
These results suggest that lipofectin-mediated gene transfer will be useful for studies of brain function, the modification of behavior and gene therapy for central nervous system disorders.
Changes in cholecystokinin mRNA expression after amygdala kindled seizures: An in situ hybridization study
1996, Molecular Brain Research
Cholecystokinin (CCK) can be a potent anticonvulsant neuropeptide in certain seizure models. Therefore, we examined whether seizures produced by electrical kindling of the amygdala or electroconvulsive seizures (ECS) would affect the expression of CCK mRNA in rat brain. Following a single kindled seizure, CCK mRNA expression was decreased about 20–58% in the amygdala. In contrast, after multiple consecutive kindled seizures, CCK mRNA expression was increased in the amygdala, cerebral cortex, CA1 pyramidal cell layer of the hippocampus and dentate hilus. A single ECS produced no effect on CCK mRNA expression, but multiple ECS increased expression in the interneurons of the hippocampus 24 h after the last seizure. Since seizures produced by ECS can be anticonvulsant to further ECS or kindled seizures, the CCK increases in the hippocampus may represent a compensatory anticonvulsant adaptation observed in both models. Overall, the kindling-induced alterations in CCK expression appear to be more complex involving multiple brain regions and distinct temporal properties.

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Effect of CCK-8 on audiogenic epileptic seizure in P77PMC rats

Abstract

Neuropharmacology

Eur J Pharmacol

Exp. Neurol.

Brain research

Neuropharmacology

Brain Res.

Neuropeptides