Abstract
IntroductionWe 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[11C]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).ResultsThe 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).ConclusionsOur 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.
Highlights
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
In this study we use 11C-Ro15-4513 positron emission tomography (PET), a marker of synaptic GABA fluxes to demonstrate that exogenous dopaminergic activation of GABA release is attenuated in the cerebral cortex of males suffering from problem gambling
This implies that GABA release is induced by exogenous dopamine in a majority of healthy controls leading to a reduction in their GABA receptor availability and this reduction is attenuated in individuals manifesting problem gambling
Summary
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 synchronisation of these oscillations is modulated by dopamine release. One of the key symptoms in behavioral and drug addiction is a problem with self-control (Ersche et al, 2012; Rømer Thomsen et al, 2013), which is closely related to another hallmark of addiction: diminished self-awareness and insight of the affected person into the severity of their disorder (Brevers et al, 2013; Goldstein et al, 2009; Moeller & Goldstein, 2014). Problems related to self-control have received most attention and empirical support in gambling disorder and drug addictions, problems related to impaired self-awareness are considered central and should receive support (Brevers et al, 2013; Brevers & Noel, 2013; Goldstein et al, 2009; Moeller & Goldstein, 2014)
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