Inducing a Tic-Like Disorder in Rats by Promoting Pallidal and Cortical Hyperexcitability

Introduction: Although described a long time ago, the pathophysiology of Tourette syndrome (TS) remains controversial. Reduced DYNergic terminals in the striatopallidal (GPe) pathway, as well as D2-DAergic hyperfunction and 5-HTergic hypofunction in both the basal ganglia and limbic system have been described in this disorder. It was hypothesized that these changes could determine GPe and cortical hyperactivity, leading to the clinical expression of tics, obsessions and compulsions. In fact, GPe-DBS has proved to be an effective treatment for TS. The present study was designed to test this hypothesis.

Methods: 50 female Wistar rats were divided into three groups: lesion group (LG), 20 animals, submitted to bilateral stereotactic electrolytic lesion of the striatum, so as to remove inhibitory efferences of the striatum to GPe (5mA/6”); sham lesion group (SG), 20 animals; pharmacological group (PG), 5 animals (received no surgery, only drugs); and control group (CG), 5 animals (no surgery, no drugs). To mimic the neurotransmitter environment, all experimental animals received, randomly, blindly and separately, two substances (8 days each): A (levodopa-benzerazide), E (levodopa-benzerazide+ergotamine+naloxone), as well as D (saline, as a pharmacological control). The animals were filmed during 4’ on the 8th day of each substance. After receiving the three substances, all surgical animals were sacrificed, and their brains removed for histopathology.

Results: Five surgical animals were discarded from analysis. Involuntary movements observed: neck extension, oromandibular movements, forepaw jerks, trunk jerks, locomotive-like, and dystonic lateral deviation. Number of animals presenting involuntary movements with each substance: CG: 0; PG: D = 0/A = 1/E = 2; SG (n = 18): D = 0/A = 4/E = 10; and LG (n = 17): D = 2/A = 17/E = 17. These differences were statistically significant (p < 0.05) between LGxSG and LGxPG, but not between SGxPG. Comparisons not statistically significant (LG): anterior × posterior striatum and left × right striatum.

Conclusions: These results seem to support the presented hypothesis. Besides, the authors propose the present study as an animal model of TS.