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Dopamine involvement in tic generation has been a long-standing focus of TS researchers. Several recent studies sought to elucidate the role of dopamine in the basal ganglia. Positron emission tomography was used to investigate striatal D2/D3 dopamine receptors using a D2/D3 receptor antagonist and an agonist with preferential binding to D3 dopamine receptors \citep{25788222} in TS subjects and controls. As expected, binding potential for the D3 preferential agonist was greater in the ventral striatum while it was greater for the D2/D3 receptor antagonist in the motor and associative regions of the dorsal striatum. However, no differences were found for these 3 regions when the TS subjects were compared with the controls, and there were no significant correlations between binding potentials and tic severity. The role of D1- and D2-type striatal activation was studied by \citet{25878272} using a Stop-signal task. D1- and D2-type activation in the dorsal, but not ventral, striatum was negatively correlated with Stop-signal reaction time. No significant correlations involving a continuous performance task were found, suggesting that different inhibitory mechanisms are involved in these two tasks. Another study examined D1 and D2 receptors in healthy adults and found that learning from positive outcomes was positively correlated with D1 receptor binding in the putamen and caudate while there was an inverted U-shaped relationship between learning from negative outcomes and D2R binding in the putamen \citep{25562824}. A dietary manipulation that reduced dopamine precursor levels significantly improved learning from negative outcomes. These results were interpreted as providing evidence that dopamine acts as a reward prediction error signal rather than as a saliency signal.  GABA involvement was studied in 23 TS children, aged 8-12, and 67 controls using a battery of vibrotactile tasks\citep{26041822}  with a subset also undergoing GABA-edited magnetic resonance spectroscopy. spectroscopy \citep{26041822}.  Lower GABA concentrations in the right sensorimotor cortex was associated with greater motor tic severity (r=-0.55). There were no significant differences between groups on reaction time and baseline amplitude discrimination threshold. Control children showed the expected increase in discrimination threshold after being exposed to a dynamically increasing subthreshold stimulus while TS children did not. The authors suggest that this is related to abnormal GABAergic inhibition although they point out that larger studies are needed to determine to what extent the high proportion of TS subjects with ADHD influenced the results. A detailed review\cite{26275849}  discusses histaminergic modulation of striatal function by the tuberomamillary nucleus of the hypothalamus. hypothalamus \cite{26275849}.  Histamine suppresses both the thalamic and cortical drive to medium-spiny projection neurons (MSNs), modulates thalamostriatal synapses resulting in a facilitation of thalamic input, and suppresses lateral feedback inhibition. The authors suggest that during wakefulness and increased attention the striatum will be more responsive to thalamostriatal input and feed-forward inhibition will predominate. The role of histamine in TS was discussed in terms of a rare mutation involving histamine synthesizing enzyme histidine decarboxylase in one TS human adult, decreased pre-pulse inhibition of startle responses, and in a rodent model an increase in a variety of amphetamine-induced stereotypies which decreased in response to histamine infusion or use of haloperidol. These effects were thought to occur as a result of the histaminergic control of the lateral GABAergic inhibitory connections between MSNs. The authors also discussed ongoing research on histaminergic treatments for TS. ### Clinical and neuropsychological studies