Abstract
Objective To evaluate the effectiveness of a rat model for comorbidity of Tourette syndrome and anxiety with empty water bottle stimulation plus iminoodipropionitrile(IDPN) injection. Methods The 48 male SD rats were randomly divided into four groups: the blank control group, the TS group, the anxiety group and the comorbidity group. The blank control group was injected with saline for 7 days. The TS group was injected with 3, 3-iminodipropionitrile (IDPN) with 250 mg/kg once a day for 7 consecutive days. The anxiety group was given empty water bottle stimulation for 21 consecutive days. The comorbidity group was given empty water bottle stimulation plus IDPN injection. At the end of the 3rd week, the behavioral changes of the stereotyped movement, elevated plus-maze and open field of the rats in each group were measured, and the contents of monoamine neurotransmitters in striatum and hippocampus were determined by HPLC. Results The results of stereotyped movement showed that there was no significant difference between the groups except for the blank control group. The elevated plus-maze test showed that the 0E/TE values of the comorbidity group (21.33±11.35) % and the anxiety group (17.68±16.89) % were significantly decreased, lower than that of the blank control group (73.24±19.33) % and TS group(61.43±21.84) %. The results of open field test showed that the total scores of open field in the comorbidity group(15.22±9.87) and anxiety group (11.17±10.76) were lower than that of the blank control group (41.86±33.30) and TS group(48.83±17.65) (P<0.01). However, there was no significant difference between the comorbidity group and the anxiety group. The test of monoamine neurotransmitters in striatum showed that the content of HIAA in the comorbidity group(0.03±0.00) ng/mg was the highest, and that of the TS group and anxiety group(0.02±0.00) ng/mg was higher than that of the blank control group (0.01±0.00) ng/mg (P<0.01). The DA test showed that the content of DA in the comorbidity group (0.03±0.00) ng/mg was the highest, and that of the comorbidity group, TS group(0.02±0.00) ng/mg and anxiety group was higher than that of the blank control group(0.01±0.00) ng/mg (P<0.01). The expression of 5-HT was most significant among the groups (P<0.01), and there was significant difference between the anxiety group((0.011±0.001) ng/mg) and the comorbidity group ((0.014±0.002) ng/mg) (P<0.01). The expression of HVA in the three model groups ((0.05±0.00) ng/mg) was higher than that in the blank group((0.02±0.00) ng/mg)(P<0.01). The expression of DOPAC in the TS group ((0.23±0.02) ng/mg) was higher than that in the blank control group((0.16±0.01) ng/mg) and comorbidity group ((0.16±0.02) ng/mg) (P<0.01). The test of monoamine neurotransmitters in hippocampus showed that the content of 5-HT in the comorbidity group((0.14±0.02) ng/mg) was the highest, followed by the anxiety group((0.1±0.03) ng/mg) and the TS group((0.07±0.04) ng/mg), which were all higher than the blank control group((0.04±0.03) ng/mg) (P<0.05, P<0.01), and there were significant differences between the comorbidity group and the TS group or anxiety group (P<0.01). The expressions of HIAA and HVA were higher in the comorbidity group((0.44±0.04)ng/mg, (0.01±0.00) ng/mg), TS group((0.46±0.15)ng/mg, (0.01±0.01) ng/mg) and anxiety group ((0.46±0.08)ng/mg, (0.01±0.00) ng/mg) than that in the blank control group((0.21±0.10)ng/mg, (0±0)ng/mg) (P<0.05, P<0.01). Conclusion This study confirms the reliability of the model and it is an ideal animal model for the study of TS with comorbidity of anxiety, which can be used for follow-up research. Key words: Uncertain empty bottle stimulation; Iminodipropionitrile; Tourette syndrome; Anxiety; Comorbidity
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