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### Pharmacological studies  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 (PET) 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. Although the authors discuss the possibility that endogenous dopamine levels might have influenced the results or that striatal dopamine receptors are involved only in a subset of TS patients, they conclude that their results challenge the widely held view that striatal dopamine receptors have a fundamental role in TS pathophysiology. Two studies examined D1 and D2 receptors in healthy adults. Striatal D1- and D2-type receptor availability was measured on stop-signal and continuous performance tasks \citep{25878272}. Stop-signal reaction time was negatively correlated with both D1- and D2-type receptor availability in the the associative and sensory motor regions of the striatum. In contrast, neither D1- nor D2-type receptor availability was associated with performance on the continuous performance task, suggesting thatthe  stop-signal and continuous performance tasks are associated with different neurochemical mechanisms related to motor response inhibition. Another In a  study of healthy adultsfound 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 (i.e., r2=0.19) 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 with a subset of the children (i.e., 19 with TS, 25 controls) also undergoing GABA-edited magnetic resonance spectroscopy \citep{26041822}. Lower GABA concentrations in the right sensorimotor cortex was were  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 discusses histaminergic modulation of striatal function by the tuberomamillary nucleus of the hypothalamus \citep{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 that,  during wakefulness and increased attention attention,  the striatum will be more responsive to thalamostriatal input and consequently  feed-forward inhibition will predominate. The role of histamine in TS was discussed in terms of a rare mutation involving histamine synthesizing enzyme enzyme,  histidine decarboxylase 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