Susceptibility of Flinders sensitive and resistant rats to pharmacologically induced seizures.

The Flinders sensitive (FSL) and Flinders resistant (FRL) line rats have been selectively bred for hyper- and hyposensitivity to the hypothermic effect of cholinergic agonists respectively. In this study, pilocarpine (250 mg/kg) and physostigmine (0.8 mg/kg) doses that are subconvulsant to outbread Sprague-Dawley rats were systemically injected to the FSL and FRL rats and a heterogenous F2 cross. All of the FRL rats developed severe motor limbic seizures in response to pilocarpine, while none of the FSL animals did. The F2 crosses showed intermediate reaction. The FRL rats were also more affected by physostigmine than the other two groups. However, the FSL rats were confirmed to be more sensitive to the hypothermic effects of pilocarpine (20 mg/kg) and physostigmine (0.6 mg/kg). Picrotoxin and kainic acid produced similar responses in the both lines, i.e., induced clonic convulsions in some animals when applied in subthreshold doses (2 and 10 mg/kg, respectively). Thus, the normally cholinergic-insensitive rats are more sensitive to the convulsant effects of high doses of cholinergic agonists, but this increased sensitivity does not extend to noncholinergic convulsants.