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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.

The addition of linoleic acid (18:2) to a solution containing oxymyoglobin (Mb II O 2 ), metmyoglobin (Mb III ), or metmyoglobin-azide complex (Mb III -N 3 − ) resulted in the formation of a common complex with identical absorption spectral properties. The addition of H 2 O 2 to a Mb III /linoleic acid mixture revealed a spectral profile with λ max at 530 nm and different from that observed in the reaction of Mb III with H 2 O 2 and identical to that of ferrylmyoglobin. This was accompanied by a progressive decrease in the absorption in the visible region, indicating heme degradation during the lipid peroxidation process. The oxidation products of linoleic acid during the Mb III /18:2/H 2 O 2 interaction were assessed by HPLC under anaerobic and aerobic conditions. In both instances, the chromatograms at λ 234nm revealed the formation of a main peak with a retention time of 11.1 min, which cochromatographed with a standard of 9-hydroperoxide of linoleic acid. The latter adduct was not degraded by the oxoferryl complex of myoglobin. The conclusions originating from this research are twofold. On the one hand, the identical spectral properties exhibited by the product originating from the reaction of either Mb II O 2 or Mb III with linoleic acid bridge the apparent discrepancy between the different reactivities of Mb II O 2 and Mb III toward H 2 O 2 and their ability to promote lipid peroxidation. On the other hand, the pattern of oxidation products of linoleic acid observed during the Mb III /H 2 O 2 interaction, i.e., the formation of a 9-hydroperoxide adduct as a major product, points to a specific binding character and a regioselectivity of the oxoferryl complex in the oxidation of unsaturated fatty acids or a catalytic preference for decomposition of the various isomeric hydroperoxides over that of the 9-hydroperoxide.