Escitalopram reversed the traumatic stress-induced depressed and anxiety-like symptoms but not the deficits of fear memory

Abstract

Rationale: Posttraumatic stress disorder (PTSD) is a trauma-induced mental disorder characterised by fear extinction dysfunction in which fear circuit monoamines are possibly associated. PTSD often coexists with depressive/anxiety symptoms, and selective serotonin reuptake inhibitors (SSRIs) are recommended to treat PTSD. However, therapeutic mechanisms of SSRIs underlying the PTSD fear symptoms remain unclear.

Objectives: Using a rodent PTSD model, we examined the effects of early SSRI intervention in mood and fear dysfunctions with associated changes of monoamines within the fear circuit areas.

Methods: A 14-day escitalopram (ESC) regimen (5 mg/kg/day) was undertaken in two separate experiments in rats which previously received a protocol of single prolonged stress (SPS). In experiment 1, sucrose preference and elevated T-maze were used to index anhedonia depression and avoidance/escape anxiety profiles. In experiment 2, the percentage of freezing time was measured in a 3-day fear conditioning paradigm. At the end of our study, tissue levels of serotonin (5-HT) in the medial prefrontal cortex, amygdala, hippocampus, and striatum were measured in experiment 1, and the efflux levels of infralimbic (IL) monoamines were measured in experiment 2.

Results: In experiment 1, ESC corrected both behavioural (depression/anxiety) and neurochemical (reduced 5-HT tissue levels in amygdala/hippocampus) abnormalities. In experiment 2, ESC was unable to correct the SPS-impaired retrieval of fear extinction. In IL, ESC increased the efflux level of 5-HT but failed to reverse SPS-reduced dopamine (DA) and noradrenaline (NA).

Conclusions: PTSD-induced mood dysfunction is psychopathologically different from PTSD-induced fear disruption in terms of disequilibrium of monoamines within the fear circuit areas.

Keywords: Anxiety; Depression; Fear memory; Posttraumatic stress disorder; Selective serotonin reuptake inhibitor; Serotonin.