Acute Fluoxetine Administration (but Not Other Antidepressant or Anxiolytics) Reverses Stress-Induced Aversive Memory Deficits in Mice

• Published in: Psychology & Neuroscience 2023-03, Vol.16 (1), p.52-70
• Main Authors: Dierschnabel, Aline Lima, de Lima, Ana Paula Nascimento, do Nascimento, Ezequiel Batista, Suchecki, Deborah, Silva, Regina Helena, Ribeiro, Alessandra Mussi
• Format: Article
• Language: English
• Subjects: Animal; Animal Learning; Antidepressant Drugs; Anxiety; Anxiolytic Drugs; Aversion; Diazepam; Drug Administration Methods; Fluoxetine; Male; Memory; Mice; Stress
• ISSN: 1984-3054; 1983-3288
• DOI: 10.1037/pne0000304

Objective: Stressful experiences stimulate the hypothalamic-pituitary-adrenal (HPA) axis, which is a main component of the physiological response to stress. When the HPA axis is acutely activated, a group of adaptive behavioral and physiological alterations occur. Notwithstanding, when it is chronically activated, adverse psychophysiological changes may take place, including deficits in cognitive functions (e.g., memory and learning) and emergence of psychiatric disorders (e.g., anxiety disorders and depression), requiring treatment with pharmacological agents. Nevertheless, current pharmacological treatments are associated with side effects and a low efficacy in some cases; moreover, there are few studies investigating the acute effects of anxiolytic and antidepressant drug on stress-induced learning and memory impairment. Thus, the aim of this study was to evaluate the effects of acute administration of antidepressant or anxiolytic drugs in stressed mice. Method: Animals were treated with diazepam (DZP), buspirone (BUS), mirtazapine (MIR) and fluoxetine (FLX), after submitted to the plus-maze discriminative avoidance task (PMDAT), an apparatus that evaluates anxiety levels concomitantly to aversive memory performance by different behavioral parameters. Results: The main results showed that stress or antidepressants drugs (BUS, MIR, and FLX) do not interfere in acquisition of the task, however, anxiolytic drug (DZP) impaired learning. In addition, acute restraint stress impaired retrieval and FLX reversed the memory deficit. Furthermore, DZP and BUS induced anxiolytic effects and MIR induced a sedative effect, while FLX had no effects on anxiety. Conclusions: Taken together, these results showed that the antidepressant FLX reversed the memory impairment produced by acute stress, suggesting a modulatory role of serotonin on the effects of stress on the consolidation of aversive memory. Public Significance Statement Stress involves a group of reactions in response to stimuli that can produce several changes in an organism, including harmful effects on learning and memory processes. The stress response is mainly mediated by secretion of glucocorticoids via the HPA axis. In adaptive conditions, stress hormones are related to glucose metabolism, regulating, storing, and mobilizing energy, to changes in the excitability of nerve cells and cognitive functions, including effects on learning and memory (Lupien & McEwen, 1997). Following acute HPA axis activation b