Examining a Hypothyroid Model of Depressive Symptoms in Mice: Tests of Behavioral Measures

There is abundant evidence suggesting that Major Depressive Disorder (MDD) is closely related to thyroid hormone (TH) function, but the exact nature of this relationship is poorly defined in the literature. The present study examined whether hypothyroidism could viably model symptoms of MDD in mice using established behavioral paradigms. It was expected that hypothyroidism would produce anhedonia-like behavior in the saccharin preference test, anxiety-like behavior in the elevated plus maze, and spatial memory impairment in the object placement task. C57BL/6J mice were randomly assigned to one of three groups, which received either a control diet, diet infused with 6-propyl-2-thiouracil (hypothyroid group), or a combination of 6-propyl-2-tiouracil and thyroxine (hyperthyroid group). Each group had ad libitum access to food and water for 4 weeks prior to behavioral assessment. Contrary to our hypothesis, hypothyroid mice did not exhibit more anhedonia or greater spatial memory impairment than controls. However, they did spend a significantly lower percentage of time in the open arms of the elevated plus-maze compared to both the control and hyperthyroid groups. Additionally, hyperthyroidism was associated with increased preference for sweetened water over tap water in the saccharin preference test. These findings raise interesting questions about how TH could regulate specific components of the depressive phenotype, which will be discussed at length. This project also lays the groundwork for a larger investigation of glutamate neurotransmission in hypothyroidism-induced depression. As a future extension of this research, AMPA receptor binding will be examined in the obtained cortical and hippocampal tissue so that relationships between depressive behaviors, thyroid status, and glutamatergic activity can be explored in a truly integrated fashion