Attenuation of dopamine‐induced GABA release in problem gamblers

Autor: Jakob Udby Blicher, Kim V. Hansen, Kim Mouridsen, Arne Møller, Hans C. Lou, David J. Brooks, Kristine Rømer Thomsen
Rok vydání: 2019
Předmět:
IMPAIRED SELF-AWARENESS
Male
Frontal Lobe/metabolism
Dopamine
Dopamine Agents
Stimulation
Paralimbic cortex
Benzodiazepines/metabolism
Synaptic Transmission
Levodopa
GABA
Benzodiazepines
Behavioral Neuroscience
0302 clinical medicine
BRAIN
gamma-Aminobutyric Acid/metabolism
Receptor
Ro15-4513
gamma-Aminobutyric Acid
Original Research
self‐control
Chemistry
05 social sciences
Dopaminergic
Dopamine Agents/administration & dosage
Frontal Lobe
ADDICTION
medicine.anatomical_structure
dopamine
medicine.drug
Adult
CORTEX
Azides
medicine.medical_specialty
self-control
Levodopa/administration & dosage
Ro15‐4513
medicine.drug_class
Synaptic Transmission/drug effects
Azides/metabolism
050105 experimental psychology
Self-Control
03 medical and health sciences
problem gambling
Double-Blind Method
DEFAULT NETWORK
Internal medicine
medicine
Humans
0501 psychology and cognitive sciences
Benzodiazepine
RECEPTOR SUBTYPE
Positron-Emission Tomography/methods
Dopamine/metabolism
GABA receptor complex
PET
Endocrinology
Positron-Emission Tomography
Gambling
Gambling/metabolism
030217 neurology & neurosurgery
Zdroj: Brain and Behavior
Møller, A, Rømer Thomsen, K, Brooks, D J, Mouridsen, K, Blicher, J U, Hansen, K V & Lou, H C 2019, ' Attenuation of dopamine-induced GABA release in problem gamblers ', Brain and Behavior, vol. 9, no. 3, e01239 . https://doi.org/10.1002/brb3.1239
ISSN: 2162-3279
DOI: 10.1002/brb3.1239
Popis: 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.
Databáze: OpenAIRE
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