Establishment and evaluation of a compound fear behavior model of Tourette’s syndrome in rats

Abstract

Background: Tourette syndrome (TS) is a common childhood disorder characterized by unwanted movements or vocal sounds called tics. It is often accompanied by other psychobehavioral disorders, including fearful behavior. The establishment and evaluation of rat models of TS and comorbid fear can provide an experimental basis for the treatment of TS and its comorbid fear disorder.Methods: Sixteen rats were randomly divided into a model group (n=8) and control group (n=8). In the model group, rats were injected intraperitoneally with iminodipropionitrile (IDPN) for 1 week to establish the TS model, which was followed by acoustic and electrical stimulation for 3 weeks to establish the rat models of TS and comorbid fear. The control group received intraperitoneal injection of saline for 1 week, and no further intervention was given in the last 3 weeks. The behavioral changes of the rats were observed and analyzed by the open field test (OFT). Protein kinase A (PKA), cyclic adenosine monophosphate (cAMP), and dopamine (DA) were measured by enzyme-linked immunosorbent assay (ELISA), and tyrosine hydroxylase (TH) and microRNA-134 (miRNA-134) in the brain tissue were detected by using polymerase chain reaction (PCR).Results: One rat in the model group died on the 24th day. Compared with the control group, the model group had significantly higher scores of locomotor activity, stereotyped behavior, and motor behavior, along with prolonged freezing time and significantly lower expression of miRNA-134. The differences in the expressions of PKA, cAMP, DA, and TH in brain tissue were not statistically significant. Conclusions:The rat models of TS and comorbid fear have similar changes in behaviors and miRNA-134 level to those in clinical settings and therefore can be used as a reliable animal model to study the mechanism of action of TS and comorbid fear.