Neuro-behavioral impact of Tourette-related striatal disinhibition in rats

Tourette syndrome has been linked to reduced GABAergic inhibition, so called neural disinhibition, in the dorsal striatum. Dorsal-striatal neural disinhibition in animal models, caused by local microinfusion of GABA-A-receptor antagonists, produces striatal local field potential (LFP) spike-wave discharges and tic-like movements resembling motor tics. Here, we characterized further the neuro-behavioral impact of striatal disinhibition, by unilateral picrotoxin infusion into the anterior dorsal striatum, in adult male Lister hooded rats. In vivo electrophysiology under anesthesia revealed enhanced neuronal burst firing in the striatum, alongside spike-wave LFP discharges. In freely moving rats, striatal picrotoxin reliably induced tic-like movements, which mainly involved lifting of the contralateral forelimb and concomitant rotational movements of head and torso, as well as occasional rotations of the whole body around its long axis. Prepulse inhibition (PPI) of the acoustic startle response was not affected, but startle reactivity tended to be reduced. Both locomotor and non-ambulatory movements, measured in photo-beam cages, were increased. Our findings suggest that, apart from generating tic-like movements, dorsal striatal disinhibition may contribute to hyperactivity, which is often comorbid with Tourette syndrome. Enhanced striatal burst firing may be important for these behavioral effects. Our findings do not support that striatal disinhibition contributes to PPI disruption, which has been associated with Tourette syndrome and suggested to contribute to tic generation.