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Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat

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Abstract

Background

Numerous studies suggest (1) that a major physiological role of brain serotonin-containing neurons is to modulate sex steroid-driven behaviour such as sex and aggression, (2) that sex steroids influence brain serotonergic neurotransmission and (3) that brain serotonergic neurotransmission displays sexual dimorphism. Such observations indicate that an important task for brain serotonin is to either enhance or counteract sex differences in behaviour.

Methods

To test this hypothesis, we explored the effect of short-term serotonin depletion on the behaviour of adult male and female rats in a behavioural paradigm in which males and females have been shown to behave differently, i.e. the elevated plus maze.

Results

Two rounds of testing of untreated Wistar rats confirmed the previous observation that females make more entries into open arms (round 1, p = 0.001; round 2, p = 0.008) and spend more time on these arms (round 1, p ≤ 0.001; round 2, p = 0.006) than males; in addition, males displayed fewer entries into closed arms upon habituation, i.e. at the second round (p ≤ 0.001) than did females. Administration of the tryptophan hydroxylase inhibitor para-chloro-phenylalanine, at a regimen (300 mg/kg/day for 3 days), markedly reducing brain content of serotonin, enhanced entries upon open arms (p = 0.01) and time spent on open arms (p = 0.004) in males but exerted no such effects in females (p = 0.9 and p = 0.9, respectively); moreover, it reduced entries into closed arms in females (p ≤ 0.001) but not in males (p = 0.1).

Conclusions

Serotonin depletion abolishing the sex differences observed at baseline supports the theory that serotonin aids to uphold certain sex differences in behaviour.

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Acknowledgments

The authors gratefully acknowledge the expert technical assistance of Ms. Inger Oscarsson and Ms. Gunilla Bourghardt. Financial support was obtained from the Swedish Research Council (2009-4746 to E.E., 2009-7006 to L.W.), Söderberg’s Foundation, Hållsten’s Foundation and the Swedish Brain Foundation. Dr. Hans Nissbrandt is gratefully acknowledged for providing equipment and know-how regarding HPLC analyses.

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The authors declare no conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology, Institute of Neuroscience and Physiology at the Sahlgrenska Academy, University of Gothenburg, Medicinaregatan 13, 413 90, Gothenburg, Sweden

    Jakob Näslund, Erik Studer, Karin Nilsson, Lars Westberg & Elias Eriksson

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  1. Jakob Näslund
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  2. Erik Studer
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  3. Karin Nilsson
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Correspondence to Jakob Näslund.

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Näslund, J., Studer, E., Nilsson, K. et al. Serotonin depletion counteracts sex differences in anxiety-related behaviour in rat. Psychopharmacology 230, 29–35 (2013). https://doi.org/10.1007/s00213-013-3133-6

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  • DOI: https://doi.org/10.1007/s00213-013-3133-6

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