Grant: Project Grant

At least half the people with epilepsy have crippling levels of fear, anxiety and depression. These emotional disturbances greatly reduce their quality of life and are not effectively treated. Thus, it is critically important that we better understand the brain mechanisms that underlie these emotional disturbances and develop effective treatments. This proposal will determine the role of the endocannabinoid (eCB) system in the emotional problems caused by repeated seizures. We will identify the brain mechanisms that become altered in epilepsy and test new cannabinoid-based drugs to determine if they can prevent or reverse the high levels of fear and anxiety. My laboratory in collaboration with several colleagues have new data which shows that the endocannabinoid system becomes altered following seizures and that this is related to emotional changes in rats. We hypothesize that alterations of fear and anxiety associated with repeated seizures are caused by a persistent maladaptation of the eCB system. We will first determine the relationship between seizure activity and endocannabinoid function with changes in emotions. We will next identify drugs which alter endocannabinoid function to determine if they can effectively block or reserve the emotional changes. Finally we will determine if high levels of stress that occurs after seizures is responsible for the emotional changes. We believe that the emotional changes that lower the quality of life in people with epilepsy can be effectively treated and that the knowledge generated by these proposed studies will ultimately improve lives for persons with epilepsy.