Attenuation of dopamine-induced GABA release in problem gamblers

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Attenuation of dopamine-induced GABA release in problem gamblers. / Møller, Arne; Rømer Thomsen, Kristine; Brooks, David J; Mouridsen, Kim; Blicher, Jakob U; Hansen, Kim V; Lou, Hans C.

In: Brain and Behavior, Vol. 9, No. 3, e01239, 03.2019.

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@article{8334a1ab2a6e4367b88de5a372fb938b,
title = "Attenuation of dopamine-induced GABA release in problem gamblers",
abstract = "INTRODUCTION: We have previously shown that an interaction between medial prefrontal and parietal cortices is instrumental in promoting self-awareness via synchronizing oscillations in the gamma range. The synchronization of these oscillations is modulated by dopamine release. Given that such oscillations result from intermittent GABA stimulation of pyramidal cells, it is of interest to determine whether the dopaminergic system regulates GABA release directly in cortical paralimbic regions. Here, we test the hypothesis that the regulation of the GABA-ergic system by the dopaminergic system becomes attenuated in problem gamblers resulting in addictive behaviors and impaired self-awareness.METHODS: [11 C]Ro15-4513 PET, a marker of benzodiazepine α1/α5 receptor availability in the GABA receptor complex, was used to detect changes in synaptic GABA levels after oral doses of 100mg L-dopa in a double-blind controlled study of male problem gamblers (N = 10) and age-matched healthy male controls (N = 10).RESULTS: The mean reduction of cortical gray matter GABA/BDZ receptor availability induced by L-dopa was significantly attenuated in the problem gambling group compared to the healthy control group (p = 0.0377).CONCLUSIONS: Our findings demonstrate that: (a) Exogenous dopamine can induce synaptic GABA release in healthy controls. (b) This release is attenuated in frontal cortical areas of males suffering from problem gambling, possibly contributing to their loss of inhibitory control. This suggests that dysfunctional dopamine regulation of GABA release may contribute to problem gambling and gambling disorder.",
keywords = "GABA, PET, Ro15-4513, dopamine, problem gambling, self-control, CORTEX, RECEPTOR SUBTYPE, DEFAULT NETWORK, ADDICTION, BRAIN, IMPAIRED SELF-AWARENESS, Humans, Male, Self-Control, Adult, Dopamine Agents/administration & dosage, Gambling/metabolism, Azides/metabolism, Double-Blind Method, Frontal Lobe/metabolism, gamma-Aminobutyric Acid/metabolism, Levodopa/administration & dosage, Synaptic Transmission/drug effects, Benzodiazepines/metabolism, Dopamine/metabolism, Positron-Emission Tomography/methods",
author = "Arne M{\o}ller and {R{\o}mer Thomsen}, Kristine and Brooks, {David J} and Kim Mouridsen and Blicher, {Jakob U} and Hansen, {Kim V} and Lou, {Hans C}",
note = "{\textcopyright} 2019 Aarhus University Hospital, Nuclear Medicine and PET. Brain and Behavior published by Wiley Periodicals, Inc.",
year = "2019",
month = mar,
doi = "10.1002/brb3.1239",
language = "English",
volume = "9",
journal = "Brain and Behavior",
issn = "2162-3279",
publisher = "JohnWiley & Sons Ltd.",
number = "3",

}

RIS

TY - JOUR

T1 - Attenuation of dopamine-induced GABA release in problem gamblers

AU - Møller, Arne

AU - Rømer Thomsen, Kristine

AU - Brooks, David J

AU - Mouridsen, Kim

AU - Blicher, Jakob U

AU - Hansen, Kim V

AU - Lou, Hans C

N1 - © 2019 Aarhus University Hospital, Nuclear Medicine and PET. Brain and Behavior published by Wiley Periodicals, Inc.

PY - 2019/3

Y1 - 2019/3

N2 - INTRODUCTION: We have previously shown that an interaction between medial prefrontal and parietal cortices is instrumental in promoting self-awareness via synchronizing oscillations in the gamma range. The synchronization of these oscillations is modulated by dopamine release. Given that such oscillations result from intermittent GABA stimulation of pyramidal cells, it is of interest to determine whether the dopaminergic system regulates GABA release directly in cortical paralimbic regions. Here, we test the hypothesis that the regulation of the GABA-ergic system by the dopaminergic system becomes attenuated in problem gamblers resulting in addictive behaviors and impaired self-awareness.METHODS: [11 C]Ro15-4513 PET, a marker of benzodiazepine α1/α5 receptor availability in the GABA receptor complex, was used to detect changes in synaptic GABA levels after oral doses of 100mg L-dopa in a double-blind controlled study of male problem gamblers (N = 10) and age-matched healthy male controls (N = 10).RESULTS: The mean reduction of cortical gray matter GABA/BDZ receptor availability induced by L-dopa was significantly attenuated in the problem gambling group compared to the healthy control group (p = 0.0377).CONCLUSIONS: Our findings demonstrate that: (a) Exogenous dopamine can induce synaptic GABA release in healthy controls. (b) This release is attenuated in frontal cortical areas of males suffering from problem gambling, possibly contributing to their loss of inhibitory control. This suggests that dysfunctional dopamine regulation of GABA release may contribute to problem gambling and gambling disorder.

AB - INTRODUCTION: We have previously shown that an interaction between medial prefrontal and parietal cortices is instrumental in promoting self-awareness via synchronizing oscillations in the gamma range. The synchronization of these oscillations is modulated by dopamine release. Given that such oscillations result from intermittent GABA stimulation of pyramidal cells, it is of interest to determine whether the dopaminergic system regulates GABA release directly in cortical paralimbic regions. Here, we test the hypothesis that the regulation of the GABA-ergic system by the dopaminergic system becomes attenuated in problem gamblers resulting in addictive behaviors and impaired self-awareness.METHODS: [11 C]Ro15-4513 PET, a marker of benzodiazepine α1/α5 receptor availability in the GABA receptor complex, was used to detect changes in synaptic GABA levels after oral doses of 100mg L-dopa in a double-blind controlled study of male problem gamblers (N = 10) and age-matched healthy male controls (N = 10).RESULTS: The mean reduction of cortical gray matter GABA/BDZ receptor availability induced by L-dopa was significantly attenuated in the problem gambling group compared to the healthy control group (p = 0.0377).CONCLUSIONS: Our findings demonstrate that: (a) Exogenous dopamine can induce synaptic GABA release in healthy controls. (b) This release is attenuated in frontal cortical areas of males suffering from problem gambling, possibly contributing to their loss of inhibitory control. This suggests that dysfunctional dopamine regulation of GABA release may contribute to problem gambling and gambling disorder.

KW - GABA

KW - PET

KW - Ro15-4513

KW - dopamine

KW - problem gambling

KW - self-control

KW - CORTEX

KW - RECEPTOR SUBTYPE

KW - DEFAULT NETWORK

KW - ADDICTION

KW - BRAIN

KW - IMPAIRED SELF-AWARENESS

KW - Humans

KW - Male

KW - Self-Control

KW - Adult

KW - Dopamine Agents/administration & dosage

KW - Gambling/metabolism

KW - Azides/metabolism

KW - Double-Blind Method

KW - Frontal Lobe/metabolism

KW - gamma-Aminobutyric Acid/metabolism

KW - Levodopa/administration & dosage

KW - Synaptic Transmission/drug effects

KW - Benzodiazepines/metabolism

KW - Dopamine/metabolism

KW - Positron-Emission Tomography/methods

U2 - 10.1002/brb3.1239

DO - 10.1002/brb3.1239

M3 - Journal article

C2 - 30788911

VL - 9

JO - Brain and Behavior

JF - Brain and Behavior

SN - 2162-3279

IS - 3

M1 - e01239

ER -