Exogenous dopamine reduces GABA receptor availability in the human brain

Background: While it has recently been shown that dopamine release stimulates conscious self-monitoring through the generation of gamma oscillations in medial prefrontal/anterior cingulate cortex, and that the GABAergic system is effective in producing such oscillations, interaction of the two transmitter systems has not been demonstrated in humans. We here hypothesize that dopamine challenge stimulates the GABA system directly in the medial prefrontal/anterior cingulate region in the human brain. Methods: Positron emission tomography (PET) with the GABA receptor alpha 1/alpha 5 subtype ligand [C-11] Ro15-4513 was used to detect changes in GABA receptor availability after clinical oral doses of levodopa in a double blind controlled study. Results: We here provide the first direct evidence for such coupling in the cerebral cortex, in particular in the medial prefrontal anterior cingulate region, by showing that exogenous dopamine decreases [C-11] Ro15-4513 binding widely in the human brain compatible with a fall in alpha 1 subtype availability in GABA complexes due to increased GABA activity.