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

Anne M. Landau; Aage Ko Alstrup; Helene Audrain; Steen Jakobsen; Mette Simonsen; Arne Møller; Poul Videbech; Gregers Wegener; Albert Gjedde; Doris J Doudet

doi:10.1177/0271678x17705260

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

Anne M. Landau, Aage Ko Alstrup, Helene Audrain, Steen Jakobsen, Mette Simonsen, Arne Møller, Poul Videbech, Gregers Wegener, Albert Gjedde, Doris J Doudet

8 Citations (Scopus)

Abstract

Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [11C]SCH23390. Seven minipigs were anesthetized and completed PET at baseline, prior to the onset of ECT treatment, and at 24-48 h and 8-10 days after the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5-week period. In all pigs, the binding of [11C]SCH23390 to striatal D1 receptors had increased by 24-48 h after ECT, and in most, binding returned towards baseline at 8-10 days. Increased binding was observed in inverse proportion to baseline binding rates. Increased binding to dopamine D1 receptors suggests facilitation of dopaminergic neurotransmission, which may contribute to the therapeutic effects of ECT. Importantly, the baseline binding capacity of D1 receptors predicts the magnitude of increased binding, up to a maximum binding capacity.

Original language	English
Journal	Journal of Cerebral Blood Flow and Metabolism
Volume	38
Issue number	5
Pages (from-to)	881-887
Number of pages	7
ISSN	0271-678X
DOIs	https://doi.org/10.1177/0271678x17705260
Publication status	Published - 1 May 2018

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title = "Elevated dopamine D1 receptor availability in striatum of G{\"o}ttingen minipigs after electroconvulsive therapy",

abstract = "Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in G{\"o}ttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [11C]SCH23390. Seven minipigs were anesthetized and completed PET at baseline, prior to the onset of ECT treatment, and at 24-48 h and 8-10 days after the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5-week period. In all pigs, the binding of [11C]SCH23390 to striatal D1 receptors had increased by 24-48 h after ECT, and in most, binding returned towards baseline at 8-10 days. Increased binding was observed in inverse proportion to baseline binding rates. Increased binding to dopamine D1 receptors suggests facilitation of dopaminergic neurotransmission, which may contribute to the therapeutic effects of ECT. Importantly, the baseline binding capacity of D1 receptors predicts the magnitude of increased binding, up to a maximum binding capacity.",

author = "Landau, {Anne M.} and Alstrup, {Aage Ko} and Helene Audrain and Steen Jakobsen and Mette Simonsen and Arne M{\o}ller and Poul Videbech and Gregers Wegener and Albert Gjedde and Doudet, {Doris J}",

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T1 - Elevated dopamine D1 receptor availability in striatum of Göttingen minipigs after electroconvulsive therapy

AU - Landau, Anne M.

AU - Alstrup, Aage Ko

AU - Audrain, Helene

AU - Jakobsen, Steen

AU - Simonsen, Mette

AU - Møller, Arne

AU - Videbech, Poul

AU - Wegener, Gregers

AU - Gjedde, Albert

AU - Doudet, Doris J

PY - 2018/5/1

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N2 - Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [11C]SCH23390. Seven minipigs were anesthetized and completed PET at baseline, prior to the onset of ECT treatment, and at 24-48 h and 8-10 days after the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5-week period. In all pigs, the binding of [11C]SCH23390 to striatal D1 receptors had increased by 24-48 h after ECT, and in most, binding returned towards baseline at 8-10 days. Increased binding was observed in inverse proportion to baseline binding rates. Increased binding to dopamine D1 receptors suggests facilitation of dopaminergic neurotransmission, which may contribute to the therapeutic effects of ECT. Importantly, the baseline binding capacity of D1 receptors predicts the magnitude of increased binding, up to a maximum binding capacity.

AB - Electroconvulsive therapy (ECT), a direct form of brain stimulation, is an effective antidepressant. We hypothesized that the beneficial effects of ECT are mediated by increased dopaminergic neurotransmission, in which the baseline activity of D1 receptors may predict the response to ECT. We established a novel model of brain stimulation in Göttingen minipigs based on the protocol of ECT applied in humans. With positron emission tomography (PET), we determined a measure of dopaminergic neurotransmission with the dopamine D1 receptor antagonist [11C]SCH23390. Seven minipigs were anesthetized and completed PET at baseline, prior to the onset of ECT treatment, and at 24-48 h and 8-10 days after the end of a clinical course of ECT, consisting of 10 ECT sessions over a 3.5-week period. In all pigs, the binding of [11C]SCH23390 to striatal D1 receptors had increased by 24-48 h after ECT, and in most, binding returned towards baseline at 8-10 days. Increased binding was observed in inverse proportion to baseline binding rates. Increased binding to dopamine D1 receptors suggests facilitation of dopaminergic neurotransmission, which may contribute to the therapeutic effects of ECT. Importantly, the baseline binding capacity of D1 receptors predicts the magnitude of increased binding, up to a maximum binding capacity.

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DO - 10.1177/0271678x17705260

M3 - Journal article

C2 - 28509598

SN - 0271-678X

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EP - 887

JO - Journal of Cerebral Blood Flow and Metabolism

JF - Journal of Cerebral Blood Flow and Metabolism

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ER -

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

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