Seizure Susceptibility in DBA and C57 Mice: The Effects of Various Convulsants

Abstract

Convulsive dose 50s (CD50s) for various convulsive drugs and minimal and maximal electroshock seizure thresholds were determined in DBA and C57 mice. DBA mice had lower maximal electroshock seizure thresholds (MESTs, 15%) and CD50s for homocysteine thiolactone (HTL, 23%) and bicuculline (69%), and a higher CD50 for pentylenetetrazol (PTZ) at 3 weeks of age, the age of maximal audiogenic seizure (AGS) susceptibility. At 8 weeks, when DBA mice are not susceptible to AGSs, significant differences were a lower minimal electroshock seizure threshold (mEST, 37%) and maximal EST (MEST) (19%), lower CD50s for N-methyl-D-aspartate (NMDA) (39%), kainic acid (KA, 50%), HTL (32%), strychnine (37%), and a higher CD50 for nicotine (55%) in DBA mice. Based on these data it is suggested that pathways involving NMDA and KA receptors are responsible for increased susceptibility to seizure initiation (mEST), and are opposed by glycine pathways, and that opposing GABA and cholinergic systems at higher CNS levels are involved in seizure spread (AGSs and MEST) in these mice. Latency patterns indicate that nicotine, strychnine, PTZ and bicuculline have high blood-brain barrier (BBB) penetrability. Picrotoxin and the excitatory amino acid receptor agonists had longer latencies, suggesting low BBB penetrability. Age-related changes in latency, however, give evidence that difficulty in drug penetration of the BBB is not responsible for differences observed in CD50s between strains.

Acute Cocaine-Induced Seizures Differential Sensitivity of Six Inbred Mouse Strains

“…Confirming several literature reports for sensitivity to KA seizures (Engstrom and Woodbury 1988;Ferraro et al 1995aFerraro et al , 1997, results showed that DBA mice were most sensitive whereas C57 mice were most resistant. A/J mice were more like C57 whereas SJL mice were more like DBA.…”

“…In order to evaluate the possibility that susceptibility to cocaine may be a more general phenomenon related to overall seizure predisposition rather than to a specific action of cocaine, strain sensitivities to kainic acid (KA) induced seizures were compared with sensitivities to cocaine-induced seizures. Confirming several literature reports for sensitivity to KA seizures (Engstrom and Woodbury 1988;Ferraro et al 1995aFerraro et al , 1997, results showed that DBA mice were most sensitive whereas C57 mice were most resistant. A/J mice were more like C57 whereas SJL mice were more like DBA.…”

“…C57 mice were never observed to exhibit abnormal electrical discharges characteristic of seizure activity whereas behavioral seizure activity in SJL and A/J was always associated with EEG spiking. These results are consistent with a large body of literature documenting that C57 mice are unique in their relatively high degree of resistance to many types of experimental seizures (Schlesinger et al 1968;Deckard et al 1976;Kellogg 1976;Engstrom and Woodbury 1988;Kosobud and Crabbe 1990;Ferraro et al 1995aFerraro et al , 1998. The study by Marley (Marley et al 1991a) relied solely upon behavioral observation for evaluation of seizure activity and it is possible that motor dysfunction such as ataxia or other involuntary movements, which we observed in cocaine-treated C57 mice, were scored as seizures.…”

“…Cocaine was injected ip over a range of doses (50-100 mg/kg) Animal models provide fundamental information regarding seizure mechanisms (Jobe et al 1973;Taylor 1976;Seyfried and Glaser 1985;Golden et al 1991Golden et al , 1995 and studies of inbred murine strains in particular (Engstrom and Woodbury 1988;Kosobud and Crabbe 1990;Kosobud et al 1992;Ferraro et al 1993Ferraro et al , 1997Frankel et al 1995b) have yielded considerable information regarding genetic influences on seizure susceptibility. Paralleling this are studies documenting substantial genetic influences in human epilepsy Leppert et al 1991;Weissbecker et al 1991;Greenberg et al 1992).…”

The role of p53 in neuronal cell death

“…Although C57BL/6 mice are known to be less susceptible to kainate-induced seizures 82,83 and seizureinduced damage, 84 Morrison and collegues 79 demonstrated significant neuronal damage in the CA3 and CA1 subregions of the hippocampus in p53 wild-type mice (129/SvEv6C57BL/6 background) despite the genetic contribution from the C57BL/6 strain. Others have also reported significant induction of neuronal damage in the CA3 and CA1 subregions of the hippocampus in C57BL/6 mice in response to kainate-induced seizures.…”