The Genetically Epilepsy-Prone Rat

LairdII, Hugh E.; Jobe, Phillip C.

doi:10.1007/978-1-59259-462-7_4

Cited by 15 publications

(6 citation statements)

References 30 publications

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“…The present study shows that sertraline decreas of the audiogenic seizures in a dose-depenc GEPR-9s. The data presented here also de systemic administration of sertraline, at the sa increased dose-dependently the extracellular 5 tions in the thalamus of freely moving GEPR ings confirm our earlier observation that drugs functional extracellular 5-HT decrease convulsion intensity in GEPRs (Laird & Jobe, 1987;Dailey et al, 1992b;Yan et al, 1994b). a Upon comparing the time courses of anticonvulsant effect with those of extracellular 5-HT concentration, we found that a negative correlation existed between extracellular 5-HT a concentration and audiogenic seizure intensity.…”

Section: Discussionsupporting

confidence: 89%

Further evidence of anticonvulsant role for 5‐hydroxytryptamine in genetically epilepsy‐prone rats

Yan¹,

Jobe²,

Dailey³

1995

British J Pharmacology

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1 This study was designed to evaluate further the role of 5-hydroxytryptamine (5-HT) in regulating susceptibility and/or intensity of audiogenic seizures in genetically epilepsy-prone rats. 2 The effects of sertraline, a highly selective and potent inhibitor of 5-HT uptake, on both the intensity of the audiogenic seizures and the extracellular concentrations of 5-HT in the thalamus were evaluated in severe seizure genetically epilepsy-prone rats. 3 Sertraline (7.5, 15 and 30 mg kg-1, i.p.) produced a dose-dependent reduction in the intensity of the audiogenic seizures. 4 Brain microdialysis studies showed that the same doses of sertraline also caused dose-dependent increases in the extracellular 5-HT concentration in the thalamus of the freely moving rats. 5 The peak anticonvulsant effect correlated temporally with the peak increases in the extracellular 5-HT concentration for this drug. 6 It is concluded that enhancement of 5-hydroxytryptaminergic transmission may contribute to the anticonvulsant effect of sertraline in severe seizure genetically epilepsy-prone rats. 7 The present results coupled with earlier investigations support the hypothesis that 5-HT plays an anticonvulsant role in genetically epilepsy-prone rats.

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Section: Discussionsupporting

confidence: 89%

Further evidence of anticonvulsant role for 5‐hydroxytryptamine in genetically epilepsy‐prone rats

Yan¹,

Jobe²,

Dailey³

1995

British J Pharmacology

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“…The present study suggests, as have others (Laird and Jobe, 1987), that multiple seizure-related pathologies occur in these animals. Numerous neural deficits are present in the GEPR.…”

Section: J E Franck Et Almentioning

confidence: 48%

“…The genetically epilepsy prone rat (GEPR) has generalized clonic-tonic convulsions to loud tone and has been reported to have an increased seizure susceptibility to a variety of nonaudiogenic convulsant treatments, including pentylenetetrazol (PTZ), electroshock (Laird and Jobe, 1987), and kindling induction to angular bundle stimulation (Savage et al, 1986). Extensive work has been done on the nature of audiogenic seizures in the GEPR; pathology has been observed in both peripheral (Penny et al, 1983) and central auditory regions which apparently culminates in decreased functional inhibition in the central nucleus of the inferior colliculus (Faingold et al, 1986a,b).…”

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confidence: 99%

Developing Genetically Epilepsy‐Prone Rats Have an Abnormal Seizure Response to Flurothyl

1989

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Development of clonic-tonic flurothyl-induced seizures was examined in both normal and genetically epilepsy-prone rats (GEPRs). At each age, from 10 to 30 days, clonus occurred at significantly shorter latencies in GEPRs than in normal rats. The latency to onset of clonic seizures did not change with age, however, in either GEPRs or normal rats. A different pattern of response was observed in the progression to tonic seizures. As normal animals matured, the latency to tonic seizures became longer and, by day 30, the duration of flurothyl exposure necessary to induce tonus was almost 70% greater in normal rats than in the GEPRs. In contrast, in GEPRs, tonic extension occurred immediately following the onset of clonus throughout development. A subset of GEPRs failed to have audiogenic seizures in a 40-day posttest. These animals had a flurothyl response identical to their audiogenic-susceptible litter mates. These data suggest that (a) a protective mechanism which develops against tonic seizures in normal rats fails to mature in the GEPR, and (b) seizure inducing gene-linked neural abnormalities occur in the GEPR independent of pathologies underlying audiogenic seizures.

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“…Chapman et al ( 1986), however, reported no significant differences in concentrations of GABA in striatum of seizure-susceptible and seizure-resistant rats, although in the present study, GABA concentrations were reduced by 41% in extracts of striaturn (caudate nucleus) of EP mice compared with ER controls ( p < 0.001). Based on pharmacological data, Laird and Jobe (1987) seizure-prone rats (Duplisse et al, 1974;Laird and Jobe, 1987), a defect in nigrostriatal GABAergic neurons might be expected to enhance the propagation of seizure activity. Lesions of the inferior colliculi abolish audiogenic seizures, whereas striatal lesions enhance seizure activity in rats (Kesner, 1966).…”

Section: Amino Acid Concentrations In E P Micementioning

confidence: 99%

Determination of Amino Acids and Monoamine Neurotransmitters in Caudate Nucleus of Seizure‐Resistant and Seizure‐Prone BALB/c Mice

Vriend

Alexiuk

Green-Johnson

et al. 1993

Journal of Neurochemistry

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Amino acid and monoamine concentrations were examined in tissue extracts of caudate nucleus of genetic substrains of BALB/c mice susceptible or resistant to audiogenic seizures. Amino acids [aspartate, glutamate, glycine, taurine, serine, gamma-aminobutyric acid (GABA)], monoamines, and related metabolites were separated by isocratic reverse-phase chromatography and detected by a coulometric electrode array system. In situ activity of tyrosine hydroxylase and tryptophan hydroxylase were determined by measuring the accumulation of L-DOPA and 5-hydroxytryptophan after administration of the decarboxylase inhibitor NSD-1015. Highly significant decreases in concentrations of both excitatory (glutamate and aspartate) and inhibitory amino acids (GABA and taurine) were observed in extracts of caudate nucleus of seizure-prone mice. Substantial decreases in concentrations of dopamine (DA) and its metabolites, 3,4-dihydroxyphenylacetic acid and homovanillic acid, were also noted. Decreased accumulation of L-DOPA after NSD-1015 administration provided evidence for decreased tyrosine hydroxylase activity and decreased DA synthesis in striatum of seizure-prone mice compared with seizure-resistant mice. Decreased concentrations of the DA metabolite 3-methoxytyramine (after NSD-1015 administration) suggested that DA release was also compromised in seizure-prone mice. No significant difference in 5-hydroxytryptophan accumulation in striatum of seizure-prone and seizure-resistant mice suggested that tryptophan hydroxylase activity and serotonin synthesis were not affected. The data suggest that seizure-prone BALB/c mice have a deficiency in intracellular content of both excitatory and inhibitory amino acids. The data also raise the issue of whether GABAergic interactions with the nigrostriatal DA system are important in the regulation of audiogenic seizure susceptibility.

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The Genetically Epilepsy-Prone Rat

Cited by 15 publications

References 30 publications

Further evidence of anticonvulsant role for 5‐hydroxytryptamine in genetically epilepsy‐prone rats

Further evidence of anticonvulsant role for 5‐hydroxytryptamine in genetically epilepsy‐prone rats

Developing Genetically Epilepsy‐Prone Rats Have an Abnormal Seizure Response to Flurothyl

Determination of Amino Acids and Monoamine Neurotransmitters in Caudate Nucleus of Seizure‐Resistant and Seizure‐Prone BALB/c Mice

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