title: Repeatedly stressed rats have enhanced vulnerability to amygdala kindling epileptogenesis.
abstract: Psychiatric disorders associated with elevated stress levels, such as depression, are present in many epilepsy patients, including those with mesial Temporal Lobe Epilepsy (mTLE). Evidence suggests that these psychiatric disorders can predate the onset of epilepsy, suggesting a causal/contributory role. Prolonged exposure to elevated corticosterone, used as a model of chronic stress/depression, accelerates limbic epileptogenesis in the amygdala kindling model. The current study examined whether exposure to repeated stress could similarly accelerate experimental epileptogenesis. Female adult non-epileptic Wistar rats were implanted with a bipolar electrode into the left amygdala, and were randomly assigned into stressed (n=18) or non-stressed (n=19) groups. Rats underwent conventional amygdala kindling (two electrical stimulations per day) until 5 Class V seizures had been experienced ('the fully kindled state'). Stressed rats were exposed to 30min restraint immediately prior to each kindling stimulation, whereas non-stressed rats received control handling. Restraint stress increased circulating corticosterone levels (pre-stress: 122±17ng/ml; post-stress: 632±33ng/ml), with no habituation observed over the experiment. Stressed rats reached the 'fully kindled state' in significantly fewer stimulations than non-stressed rats (21±1 vs 33±3 stimulations; p=0.022; ANOVA), indicative of a vulnerability to epileptogenesis. Further, seizure durations were significantly longer in stressed rats (p<0.001; ANOVA). These data demonstrate that exposure to repeated experimental stress accelerates the development of limbic epileptogenesis, an effect which may be related to elevated corticosterone levels. This may have implications for understanding the effects of chronic stress and depression in disease onset and progression of mTLE in humans.
authors: Department of Medicine (Royal Melbourne Hospital), University of Melbourne, Parkville, VIC, Australia. ncjones@unimelb.edu.au
authors: Nigel C
authors: NC
authors: Jones
authors: Han Ee
authors: HE
authors: Lee
authors: Meng
authors: M
authors: Yang
authors: Sandra M
authors: SM
authors: Rees
authors: Margaret J
authors: MJ
authors: Morris
authors: Terence J
authors: TJ
authors: O'Brien
authors: Michael R
authors: MR
authors: Salzberg
mesh_terms: D000679:Amygdala / Q000502:physiology*; D000818:Animals; D003345:Corticosterone / Q000378:metabolism; D004195:Disease Models, Animal; D004558:Electric Stimulation / Q000379:methods; D004827:Epilepsy / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006185:Habituation, Psychophysiologic / Q000502:physiology; D007696:Kindling, Neurologic / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012149:Restraint, Physical / Q000379:methods / Q000502:physiology; D013315:Stress, Psychological / Q000097:blood / Q000150:complications / Q000503:physiopathology*
chemical_list: D003345:Corticosterone