, Volume 178, Issue 2–3, pp 151–160 | Cite as

Differences in the effects of 5-HT1A receptor agonists on forced swimming behavior and brain 5-HT metabolism between low and high aggressive mice

  • Alexa H. Veenema
  • Thomas I. F. H. Cremers
  • Minke E. Jongsma
  • Peter J. Steenbergen
  • Sietse F. de Boer
  • Jaap M. Koolhaas
Original Investigation



Male wild house-mice genetically selected for long attack latency (LAL) and short attack latency (SAL) differ in structural and functional properties of postsynaptic serotonergic-1A (5-HT1A) receptors. These mouse lines also show divergent behavioral responses in the forced swimming test (FST, i.e., higher immobility by LAL versus SAL mice).


We investigated whether the line difference in 5-HT1A receptors is associated with a difference in brain 5-HT metabolism, and whether acute administration of a 5-HT1A receptor agonist could differentially affect the behavioral responses of LAL and SAL mice.


5-HT and 5-hydroxyindoleacetic acid (5-HIAA) levels were measured in homogenates of several brain regions using high-performance liquid chromatography. The behavioral effect of the full 5-HT1A receptor agonist, 8-OH-DPAT, and of the somatodendritic 5-HT1A autoreceptor agonist, S-15535, was examined in the FST. The effect of 8-OH-DPAT on forced swimming-induced 5-HT metabolism in brain homogenates was determined.


In most brain regions, 5-HT and 5-HIAA levels and 5-HT turnover were not significantly different between LAL and SAL mice. 8-OH-DPAT abolished the behavioral line difference in the FST by reducing immobility in LAL mice and reducing climbing in SAL mice. S-15535 induced a similar behavioral effect to 8-OH-DPAT in SAL mice, but did not alter the behavior of LAL mice. Compared with LAL, forced swimming elicited in SAL mice a higher brain 5-HT turnover, which was potently attenuated by 8-OH-DPAT.


It is unlikely that the difference in 5-HT1A properties between LAL and SAL mice is an adaptive compensatory reaction to changes in 5-HT metabolism. Although unspecific motor effects, at least in SAL mice, cannot be ruled out, it is suggested that the behavioral effects of 8-OH-DPAT and S-15535 may be mediated by predominant activation of postsynaptic 5-HT1A receptors in LAL mice and by presynaptic 5-HT1A receptors in SAL mice.


Behavior Forced swimming test 8-OH-DPAT Serotonin (5-HT) Stress 5-HT1A receptor S-15535 


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Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  • Alexa H. Veenema
    • 1
    • 2
  • Thomas I. F. H. Cremers
    • 3
  • Minke E. Jongsma
    • 3
  • Peter J. Steenbergen
    • 4
  • Sietse F. de Boer
    • 1
  • Jaap M. Koolhaas
    • 1
  1. 1.Department of Animal Physiology, Center for Behavioral and Cognitive NeurosciencesUniversity of GroningenGroningenThe Netherlands
  2. 2.Institute for ZoologyUniversity of RegensburgRegensburgGermany
  3. 3.Department of PsychiatryGroningen University HospitalGroningenThe Netherlands
  4. 4.Division of Medical Pharmacology, Leiden/Amsterdam Center for Drug ResearchLeiden University Medical CenterLeidenThe Netherlands

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