We propose to pharmacologically modify seizure length in animals receiving electroconvulsive stimulation (ECS), a well-characterized animal analogue of electroconvulsive therapy (ECT). ECT is an effective clinical treatment in severe psychiatric illnesses that requires a seizures for its therapeutic benefit. In ECT, caffeine pretreatment increases seizure duration and enhances clinical efficacy. However, the mechanisms by which seizures exert their effects and the neurochemical consequences of caffeine-augmented seizures have not been studied. In our initial studies, caffeine lengthened ECS seizures in rats in a dose-dependent manner. Caffeine had a sustained effect over a series of daily ECS, augmented the typical ECS-induced decrease in Beta-adrenergic receptors and prevented the typical ECS-induced increase in 5-HT-2 serotonin receptors. We propose to study drug-modified ECS to characterize caffeine augmentation of ECS and test whether increased seizures length determines the neurochemical consequences of modified seizures. In addition, we will use more selective drugs and inbred strains of rodents with differing seizure characteristics to define which pharmacological action of caffeine is important for the neurochemical change. An improved understanding of the neurochemistry of electroconvulsive seizures may allow for improvements in clinical ECT as well as design of additional psychopharmacological treatments of psychiatric conditions.
| Francis, A; Fochtmann, L (1995) Reduced proconvulsant activity of caffeine in rats after a series of electroconvulsive seizures. Psychopharmacology (Berl) 119:99-104 |
