Seizure susceptibility in DBA and C57 mice: the effects of various convulsants.
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.
Engstrom
F L
FL
Department of Physiology, University of Utah School of Medicine, Salt Lake City 84108.
Woodbury
D M
DM
D000161:Acoustic Stimulation; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives / Q000378:metabolism; D001640:Bicuculline / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects; D003292:Convulsants / Q000378:metabolism* / Q000494:pharmacology; D004198:Disease Susceptibility; D004597:Electroshock; D006710:Homocysteine / Q000031:analogs & derivatives / Q000378:metabolism; D007608:Kainic Acid / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016202:N-Methylaspartate; D009538:Nicotine / Q000378:metabolism; D010433:Pentylenetetrazole / Q000378:metabolism; D010852:Picrotoxin / Q000378:metabolism; D012640:Seizures / Q000209:etiology / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001224:Aspartic Acid; D001640:Bicuculline; D003292:Convulsants; D006710:Homocysteine; D007608:Kainic Acid; D016202:N-Methylaspartate; D009538:Nicotine; D010433:Pentylenetetrazole; D010852:Picrotoxin; D005680:gamma-Aminobutyric Acid; C007957:homocysteine thiolactone