Abstract:
:Inbred mouse strains differed significantly in sensitivity to convulsions induced by 9 convulsant drugs administered using a timed infusion procedure. Some strains (e.g. BALB/cJ, A/J) were generally seizure-susceptible, while some were generally seizure resistant (e.g. C57BL/6J, SWR/J). However, the overall pattern of strain sensitivities was complex, and depended upon drug and convulsant sign. Five of the drugs (bicuculline, DMCM, picrotoxin, TBPS and pentylenetetrazol (PTZ] produce convulsions, at least in part, through their interactions with the GABA receptor, while the other 4 (strychnine, CHEB, 4-aminopyridine and kainic acid) act through independent mechanisms. We predicted that responses to drugs with similar mechanisms of action would be genetically correlated. However, strains sensitive to picrotoxin-induced convulsions were not necessarily sensitive to convulsions elicited by PTZ or TBPS. Furthermore, different convulsant signs produced by a single drug were not always strongly correlated. Instead, genetic correlations were found among inbred strains for sensitivity to similar convulsant signs produced by different drugs. This suggests that genetic variation in sensitivity to these convulsant drugs arises primarily from variation in systems important for the expression of the convulsion.
journal_name
Brain Resjournal_title
Brain researchauthors
Kosobud AE,Crabbe JCdoi
10.1016/0006-8993(90)90243-5subject
Has Abstractpub_date
1990-08-27 00:00:00pages
8-16issue
1eissn
0006-8993issn
1872-6240pii
0006-8993(90)90243-5journal_volume
526pub_type
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