Antiparkinsonian Mechanism of Electroconvulsive Therapy in MPTP-Lesioned Non-Human Primates

Abstract

Background: Electroconvulsive therapy (ECT), an effective treatment for depression, also improves motor symptomatology in Parkinson’s disease (PD). We have previously demonstrated that ECT stimulates dopamine (DA) function in the striatum of healthy non-human primates, suggesting that DA may contribute to antidepressant effects. Objective: We investigated the potential role of DA mechanisms in the amelioration of PD symptoms following a clinical course of ECT. Methods: We treated non-human primates rendered mildly bilaterally or unilaterally parkinsonian with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), with a course of 6 ECT treatments. Using positron emission tomography, animals were scanned at baseline and at various time points after ECT with tracers of the DA system. Data were analyzed using the Logan reference tissue model and statistics were performed using orthogonal polynomial contrasts. Results: There was no change in binding of the DA transporter tracer in the lesioned striata after ECT as opposed to what we measured in the striatum of healthy animals. Raclopride binding to the D_2/3 receptors was unaffected in all groups. However, there were increases in vesicular monoamine transporter type 2 and D₁ receptor binding in the MPTP-lesioned striata after ECT, returning towards baseline by 6 weeks. Conclusion: We suggest that the effects of ECT in PD may proceed from a mechanism similar to that in healthy animals but with a blunted dopaminergic response, likely due to the significant loss of striatal DA terminals. The safety of ECT, its mild side effects and its stimulatory effects of the DA system may thus make it an attractive adjunct to antiparkinsonian treatment.

Elevated dopamine D1 receptor availability in striatum of Göttingen minipigs after electroconvulsive therapy

“…It also appears that the increase of DA D1 receptor binding capacity is a consequence of plasticity mechanisms that are the result of release of one or more other monoamines. 10,11,21,46 In summary, a clinical course of bilateral ECT in ECT-naı¨ve minipigs increases dopamine D1 binding capacity, a response which may be associated with antidepressant effects in patients with depression or PD. We provided evidence that the baseline binding capacity of D1 receptors in the minipigs predict the magnitude of increased binding, up to a maximum binding capacity.…”

“…It also appears that the increase of DA D1 receptor binding capacity is a consequence of plasticity mechanisms that are the result of release of one or more other monoamines. 10,11,21,46…”

“…Studies of non-human primates in vivo by the present group of researchers reveal increased DAergic signaling, linked to increased receptor availability after ECT. 10,11 In these studies, DAergic stimulation is the habitual response to ECT or electroconvulsive stimulation (ECS, the rodent equivalent of ECT), independently of the antidepressant effect. At first, the response of the DA system was observed in patients with PD, in whom the antiparkinsonian effect occurs almost immediately following ECT initiation.…”

Electroconvulsive Therapy for Parkinson's Disease: A Systematic Review and Meta‐Analysis

“…Modulation of dopaminergic pathways may explain the effect of ECT on PD's motor manifestations. According to animal studies, ECT increased D1 and D3 binding in the striatum, 51 and ECT increased D1 receptor binding and vesicular monoamine transporter type 2 binding 52 . In human studies, ECT increased homovanillic acid in the cerebrospinal fluid of PD patients, 26 whereas ECT did not change the dopamine transporter system measured using single‐photon emission computed tomography 28 .…”

“…According to animal studies, ECT increased D1 and D3 binding in the striatum, 51 and ECT increased D1 receptor binding and vesicular monoamine transporter type 2 binding. 52 In human studies, ECT increased homovanillic acid in the cerebrospinal fluid of PD patients, 26 whereas ECT did not change the dopamine transporter system measured using single-photon emission computed tomography. 28 One would expect that increases in dopamine caused by ECT could worsen psychotic symptoms.…”