Evaluation of Cognitive Status and Long-Term Thyroid Functions in Methimazole-induced Rat Hypothyroidism Model

Abstract

Methimazole, a widely used agent in the treatment of hyperthyroidism, is also used to induce hypothyroidism in experimental studies. In this study, we aimed to evaluate cognitive functions in a methimazole-induced rat hypothyroidism model and also to determine long-term thyroid functions. Twelve adult female/male Wistar rats (250-300 g) were randomly divided into two groups, one of which was given 0.02% methimazole in drinking water for 4 weeks, as the other group was given normal water. After 4 weeks, Morris water maze, elevated plus maze, tail suspension test, passive avoidance test were applied. Serum free T4 and TSH levels were measured 8 weeks after discontinuation of methimazole, and thyroid tissue was evaluated histopathologically. There was no significant difference between the groups in the Morris water maze and passive avoidance test (p > 0.05). In the elevated plus maze, hypothyroid rats spent more time in the open-field (123.5  35.5 sec vs. 12.5  7.9 sec; p = 0.012); made more entries into the open and middle area (3.0  0.4 vs. 0.7  0.5; p = 0.006 and 6.2  1.2 vs. 2.8  0.7; p = 0.042, respectively). In the tail suspension test, the duration of immobility was significantly longer in the hypothyroid group (186.2  19.5 sec vs. 110.3  26.2 sec; p = 0.043). In the histopathological examination, colloid vacuolization was observed in the hypothyroid group, but serum free T4 and TSH levels did not show difference between the groups. In conclusion, methimazole-induced hypothyroidism decreases anxiety and increases tendency to depression without impairing learning and memory. Additionally, although thyroid follicle distortion is observed histopathologically, serum thyroid functions return to normal in the long-term. On this basis, further studies should be planned to elucidate the relationship between hypothyroidism and cognitive functions.