Rationale: The cognitive impairments apparent in many depressed patients appear to be alleviated by chronic treatments with antidepressants. However, evaluation of antidepressant treatments in rodents rarely includes investigation of their effects on cognitive performance.
Objectives: The aim of this study was to investigate in rat the effects of paroxetine, a selective serotonin reuptake inhibitor antidepressant, and imipramine, a tricyclic antidepressant, on learning and memory in spatial and non-spatial tasks.
Materials and methods: Adult male Sprague-Dawley rats weighing 230-250 g were used in two sets of experiments.
Results: Spatial working memory was first tested in a radial-arm maze using the delayed spatial win-shift task. During the course of a 10-day treatment, paroxetine-treated rats (10 mg/kg) did not show any deficit in memory performance. Conversely, imipramine-treated rats (10 mg/kg) made significantly more errors than controls. Secondly, we tested temporal order memory for objects. Rats received one injection or chronic injections (28 days) of imipramine (10 mg/kg), paroxetine (10 mg/kg) or saline. In contrast to controls, on the day after the acute injection, both imipramine- and paroxetine-treated rats were unable to discriminate the old from the recent objects. After chronic treatment, the imipramine-treated rats were unable to differentiate between the two objects, whereas paroxetine-treated rats, as controls, spent more time exploring the old one. When the delay before the test phase was increased to 4 h, controls could not discriminate the objects, whereas rats treated for 28 days with paroxetine were able to distinguish the old from the recent object.
Conclusions: In contrast to the persistent harmful effects of imipramine, chronic treatment with paroxetine does not alter spatial working memory performance and appears to improve temporal order memory performance.