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

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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.

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Acknowledgments

This study was supported by grants from the Ministry of Science and Technology (MOST 102-2410-H-016-002 and 103-2410-H-016-004) and National Defense Medical Center (D101-15-3 and 103-M085) of Taiwan. Special thanks must go to Lundbeck company, Denmark for kindly providing the ESC.

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Authors and Affiliations

  1. Department of Physiology and Biophysics, National Defense Medical Center, Taipei, 11490, Taiwan

    Chen-Cheng Lin & Yia-Ping Liu

  2. Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, 11490, Taiwan

    Yia-Ping Liu

  3. Division of Medical Research and Education, Cheng Hsin General Hospital, Taipei, 11220, Taiwan

    Che-Se Tung

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  1. Chen-Cheng Lin
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Correspondence to Yia-Ping Liu.

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Lin, CC., Tung, CS. & Liu, YP. Escitalopram reversed the traumatic stress-induced depressed and anxiety-like symptoms but not the deficits of fear memory. Psychopharmacology 233, 1135–1146 (2016). https://doi.org/10.1007/s00213-015-4194-5

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  • DOI: https://doi.org/10.1007/s00213-015-4194-5

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