Rats bred for susceptibility to depression-like phenotypes have higher kainic acid-induced seizure mortality than their depression-resistant counterparts.

Epidemiological evidence suggests that epilepsy and depression are comorbid diseases. In fact, depression is the most common neuropsychiatric disorder associated with epilepsy, particularly temporal lobe epilepsy, and individuals with a history of depression are at a higher risk for developing epilepsy than the general population. Despite the epidemiological evidence for this link, there has been little experimental evidence to support the connection or elucidate possible underlying mechanisms. In an effort to address this problem and develop an animal model of epilepsy and depression comorbidity, we assessed seizure susceptibility and severity parameters in rats selectively bred for either susceptibility (the SwLo, SUS, and HYPER lines) or resistance (the SwHi, RES, and MON RES lines) to depression-like phenotypes. We found that rats bred for susceptibility to depression-like phenotypes experienced higher mortality following kainic acid-induced seizures than their resistant counterparts. In contrast, most line differences were not recapitulated when flurothyl was used to elicit seizures. Stress reduced kainic acid-induced mortality rates in all lines except the HYPER rats, supporting previously established indications that the stress response of HYPER rats is abnormal. These combined results support a neurobiological link between epilepsy and depression, advancing us towards an animal model of their comorbidity.