Authors :
Presenting Author: Renaud Gom, BS – Hotchkiss Brain Institute
Antis George, PhD – Hotchkiss Brain Institute; Sydney Harris, MSc – Hotchkiss Brain Institute; Hill Matthew, PhD – Hotchkiss Brain Institute; Roberto Colangeli, PhD – Hotchkiss Brain Institute; Cam Teskey, PhD – Hotchkiss Brain Institute
Rationale:
Up to half of people with epilepsy suffer from emotional comorbidities, including depression and anxiety disorders, which can severely impair quality of life. Alterations in emotionality following repeated seizures have previously been linked to endocannabinoid system dysfunction. The aim of this study was to determine whether activation of the hypothalamic-pituitary-adrenal (HPA) axis following seizures mediates the changes in endocannabinoid levels and fear and anxiety behavior.Methods:
Young adult Long-Evans rats were stereotaxically implanted with bipolar stimulating electrodes in the right basolateral amygdala (BLA). Seizures were elicited at a suprathreshold current on a fixed schedule and either metyrapone, a corticosterone synthesis inhibitor, or vehicle was administered prior to each seizure. In addition to measuring fear behavior and CORT concentration, we also measured seizure thresholds, seizure severity, seizure duration, and endocannabinoid levels were collected. Results:
Plasma corticosterone levels were highly elevated after seizures, however no long-term changes in baseline corticosterone were observed during the 2-week kindling process. Pre-seizure metyrapone administration completely prevented seizure-induced corticosterone increases. Rats administered vehicle and had seizures showed impaired fear memory retention at 24 and 48 hours after auditory fear conditioning relative to non-seizure controls. Impaired memory retention did not occur in rats administered metyrapone prior to each seizure.Conclusions:
These experiments illustrate that an increase in HPA axis activation following seizures result in changes in fear processing and memory and could be targeted in future treatments of comorbid psychiatric conditions in people with epilepsy.
Funding:
CIHR, University of Calgary.