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Acute escitalopram but not contextual conditioning exerts a stronger “anxiogenic” effect in rats with high baseline “anxiety” in the acoustic startle paradigm

Abstract

Rationale

Acute administration of selective serotonin reuptake inhibitors (SSRIs) may enhance anxiety in humans, those with anxiety disorders being more susceptible than others. Fear-conditioned or unconditioned acoustic startle and freezing are common measures of fear and/or “anxiety” in rodents that may be used to study this effect of SSRIs preclinically.

Objectives

Our aim was to shed further light on the effect of acute administration of an SSRI, escitalopram (10 mg/kg), on startle and freezing in the absence or presence of prior contextual conditioning. Repeated testing also enabled us to evaluate (i) if there are stable inter-animal variations with respect to these parameters in a batch of outbred Wistar rats, (ii) the possible relationship between the two and (iii) if baseline behaviour predicts the response to escitalopram.

Results

Inter-animal test-retest correlations were found for both startle and freezing at baseline, and the two parameters also correlated with each other. Both escitalopram and contextual conditioning increased freezing and startle but without exerting any synergistic effect. While animals displaying high startle at baseline showed higher susceptibility to respond to escitalopram, the effect of conditioning was more pronounced in those with low baseline startle.

Conclusions

The results support the usefulness of both conditioned and non-conditioned startle and freezing to capture an “anxiogenic” influence of SSRIs. Also, they suggest that baseline non-conditioned startle may predict this response in a manner reflecting the clinical situation in the sense that subjects with high baseline “anxiety” are particularly prone to respond with enhanced “anxiety” following acute SSRI administration.

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Acknowledgments

Inger Oscarsson and Gunilla Bourghardt are acknowledged for excellent technical assistance. The Swedish Research Council (K2013-61X-14961-07-3), Söderberg’s Foundation (MT-30/09), Hållsten’s Foundation and the Swedish Brain Foundation (FO-20110293) are acknowledged for financial support of the research described in this report.

Conflict of interest

None of the authors declare any conflict of interest.

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Correspondence to Elias Eriksson.

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Pettersson, R., Näslund, J., Nilsson, S. et al. Acute escitalopram but not contextual conditioning exerts a stronger “anxiogenic” effect in rats with high baseline “anxiety” in the acoustic startle paradigm. Psychopharmacology 232, 1461–1469 (2015). https://doi.org/10.1007/s00213-014-3783-z

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  • DOI: https://doi.org/10.1007/s00213-014-3783-z

Keywords

  • Serotonin
  • Selective serotonin reuptake inhibitor (SSRI)
  • Anxiety disorder
  • Freezing
  • Startle
  • Fear conditioning
  • Contextual fear