Bupropion and Citalopram in the APP23 Mouse Model of Alzheimer's Disease: A Study in a Dry-Land Maze

Abstract

Background. Incipient Alzheimer's disease is often disguised as depressive disorder. Over the course of AD, depressive symptoms are even more frequent. Hence, treatment with antidepressants is common in AD. It was the goal of the present study to assess whether two common antidepressants with different mechanisms of action affect spatial learning in a transgenic animal model of Alzheimer's disease. Methods. We assessed spatial memory of male wild-type and B6C3-Tg(APPswe,PSEN1dE9)85Dbo (APP23) transgenic animals in a complex dry-land maze. Animals were treated with citalopram (10 mg/kg) and bupropion (20 mg/kg). Results. Moving and resting time until finding the goal zone decreased in 4.5-month-old sham-treated wild-type animals and, to a lesser extent, in APP23 animals. Compared with sham-treated APP23 animals, treatment with bupropion reduced resting time and increased speed. On treatment with citalopram, moving and resting time were unchanged but speed decreased. Length of the path to the goal zone did not change on either bupropion or citalopram. Conclusion. Bupropion increases psychomotor activity in APP23 transgenic animals, while citalopram slightly reduces psychomotor activity. Spatial learning per se is unaffected by treatment with either bupropion or citalopram.

Figure 1

Aerial view of the complex maze. Animals were placed in the start zone. A video-tracking system (cf. Section 2) registered the location of the animals' position at a frequency of 1 Hz.

Figure 2

Running speed (a) and learning curve for the distance (b) to escape from the complex maze. Values represent means and standard errors for a group of wild-type animals (n = 7, open squares) and APP23 animals (n = 6, filled squares), both sham treated. Values represent means ± standard errors.

Figure 3

Learning curve for the time to escape from the complex maze in APP23 animals sham treated (n = 6, filled squares), APP23 animals treated with bupropion (n = 7, filled triangles), or APP23 animals treated with citalopram (n = 6, filled circles). Values represent means ± standard errors.

Figure 4

Running speed (a) and learning curve for distance (b) to escape from the complex maze in APP23 animals sham treated (n = 6, filled squares), APP23 animals treated with bupropion (n = 7, filled triangles), or APP23 animals treated with citalopram (n = 6, filled circles). Values represent means ± standard errors.