The effects of electroconvulsive therapy in an animal model of Parkinson’s Disease : mechanisms of a potential adjunct treatment

Electroconvulsive therapy (ECT) is a widely used and effective treatment for mood disorders. ECT also appears to have positive effects in Parkinson’s disease (PD), improving motor symptoms for several weeks. Some of the most consistent effects of electroconvulsive shock (ECS) in animals are enhancement of both monoamine neurotransmission and neurotrophic factor concentrations in limbic brain regions. We hypothesized that the mechanism of action of ECT in PD is similar to its proposed mechanism of action in depression, more specifically, that ECS in 6-hydroxydopamine (6-OHDA)-lesioned rats will: (1) improve motor behaviour; (2) enhance D₁ and D₃ (without changing D₂) receptor binding; and (3) enhance striatal neurotrophic factor concentrations. We performed several pilot and validation studies to determine the appropriate animal models (non-human primate vs. rat model of PD) and to develop tools to investigate our hypotheses with (autoradiography with positron-emitting tracers and non-pharmacological motor evaluation). To examine our three specific hypotheses, we treated 6-OHDA-lesioned rats with ECS or sham treatment and examined their motor behaviour using two non-pharmacological behavioural tests; the Cylinder Test, which evaluates forelimb function, and the Tapered/Ledged Beam-Walking Test, which examines hindlimb function. After the course of ECS or sham treatment, the animals were sacrificed, and their brains were removed and processed for either dopamine receptor binding or neurotrophic factor concentration. ECS treatment significantly improved hindlimb function, but had no apparent impact on forelimb function. ECS treatment also enhanced striatal D₁ and D₃ receptor binding, without affecting D₂ binding. Finally, repeated ECS treatment decreased brain-derived neurotrophic factor (BDNF) concentrations in the prefrontal cortex (PFC), but increased BDNF in the hippocampus and striatum. Basic fibroblast growth factor (FGF-2) concentrations were increased in the striatum, whereas glial cell line-derived neurotrophic factor protein was significantly decreased in the PFC. This body of work provides the first thorough investigation of the effects of repeated ECS treatment in the 6-OHDA-lesioned rat, showing that it improves motor function, enhances DA neurotransmission via upregulation of the D₁ and D₃ receptors, and increases striatal BDNF and FGF-2, and the results support the continued use and study of ECT as an adjunctive treatment for PD.Medicine, Faculty ofGraduat