Evaluation of Cognitive Functions, Anxiety- and Depression-Like Behaviours in Methimazole-Induced Rat Hypothyroidism Model: A Pilot Study

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 and anxiety- and depression-like behaviours in a methimazole-induced rat hypothyroidism model. 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 was applied. Serum free T4 and TSH levels were measured 8 weeks after discontinuation of methimazole, and thyroid tissue was evaluated histopathologically. In the Morris water maze test, a significant difference was observed between the groups only on the 1st day (p < 0.001). There was no significant difference between the groups in the passive avoidance test (p = 0.477). 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. On this basis, further studies should be planned to elucidate the relationship between hypothyroidism and cognitive functions.

Keywords

• Hypothyroidism
• Cognitive Function
• Rat
• Methimazole

Metimazol ile Oluşturulan Sıçan Hipotiroidi Modelinde Kognitif Fonksiyonlar, Anksiyete ve Depresyon Benzeri Davranışların Değerlendirilmesi: Pilot Çalışma

Abstract

Hipertiroidizm tedavisinde yaygın olarak kullanılan metimazol, deneysel çalışmalarda geçici hipotiroidizm modeli oluşturmak için kullanılmaktadır. Çalışmamızda metimazol ile oluşturulan sıçan hipotiroidi modelinde kognitif fonksiyonların değerlendirilmesi ve hipotiroidinin anksiyete ve depresyon benzeri davranışlar üzerine etkisinin belirlenmesi amaçlanmıştır. Oniki adet erişkin dişi/erkek Wistar sıçan (250-300 g) iki gruba ayrılarak bir gruba 4 hafta süre ile içme suyu içinde %0,02 metimazol verilerek hipotiroidizm oluşturulmuş, diğer gruba normal içme suyu verilmiştir. Dört hafta sonunda, Morris su labirenti, yükseltilmiş artı labirent, kuyruk suspansiyon testi, pasif sakınma testi uygulanmıştır. Metimazol kesildikten 8 hafta sonra serum serbest T4 ve TSH düzeyleri ölçülmüş ve tiroid dokusu histopatolojik olarak değerlendirilmiştir. Morris su labirenti testinde sadece 1. günde gruplar arasında anlamlı fark izlenmiştir (p < 0,001). Pasif sakınma testinde ise gruplar arasında anlamlı fark görülmemiştir (p = 0,477). Yükseltilmiş artı labirentte hipotiroid sıçanlar açık alanda daha fazla süre geçirmiş (123,5 ± 35,5 sn vs. 12,5 ± 7,9 sn; p = 0,012); açık ve orta alana daha fazla sayıda giriş yapmıştır (sırasıyla, 3,0 ± 0,4 vs. 0,7 ± 0,5; p = 0,006, 6,2 ± 1,2 vs. 2,8 ± 0,7; p = 0,042). Kuyruk suspansiyon testinde hipotiroid grubun hareketsiz kaldığı süre, ötiroid gruba göre anlamlı olarak daha uzun bulunmuştur (186,2 ± 19,5 sn vs. 110,3 ± 26,2 sn; p = 0,043). Histopatolojik incelemede, hipotiroid grubunda kolloid vakuolizasyonu izlenmiş, ancak serum serbest T4 ve TSH düzeylerinde gruplar arasında fark görülmemiştir. Sonuç olarak, sıçanda metimazol hipotiroidi modeli öğrenme ve bellekte bozulma oluşturmaksızın, anksiyeteyi azaltıp depresyona eğilimi artırmaktadır. Bu zeminde, hipotiroidi ve kognitif fonksiyon ilişkisini aydınlatmaya yönelik ileri çalışmalar planlanmalıdır.

Keywords

• Hipotiroidizm
• Kognitif fonksiyon
• Sıçan
• Metimazol

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