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Psychopharmacology

, Volume 110, Issue 1–2, pp 53–59 | Cite as

The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice

  • Connie Sánchez
  • Jørn Arnt
  • John Hyttel
  • Ejner K. Moltzen
Original Investigations

Abstract

The role of serotonergic (5-HT) receptor subtypes in mediation of aggressive behaviour in isolated male mice has been studied. Increase of attack latency was used as a simple measure of antiaggressive behaviour. 5-HT1A agonists (BAY R 1531, 8-OHDPAT, flesinoxan, gepirone, 5MeO DMT, buspirone, ipsapirone, BMY 14802) completely inhibit the aggressive behaviour irrespective of their intrinsic activities. Also the putative antagonists spiroxatrine and NAN 190 as well as the non-selective 5-HT1 agonists RU 24969, TFMPP, mCPP and eltoprazine have an antiaggressive effect. The mixed 5-HT1A andβ-adrenoceptor antagonists (−)-alprenolol and pindolol are ineffective and do not inhibit the effect of 8-OHDPAT. Neither does the non-selective 5-HT antagonist metergoline. The antiaggressive effect correlates with 5-HT1A receptor affinity in vitro and with generalization to the 8-OHDPAT-induced discriminative stimulus. The selective 5-HT uptake inhibitor citalopram does not inhibit aggressive behaviour. The 5-HT2 agonist DOI has an antiaggressive effect only at high doses, whereas the 5-HT2 antagonist ritanserin and the 5-HT3 antagonist ondansetron are ineffective. Prazosin (α1-adrenoceptor antagonist), clonidine (α2-adrenoceptor agonist), clenbuterol (β-adrenoceptor agonist), ketanserin (5-HT2 receptor andα1-adrenoceptor antagonist), clozapine and (−)-octoclothepin (dopamine (DA), 5-HT2 receptor andα1-adrenoceptor antagonist) all show an antiaggressive effect. SCH 23390 (DA D1 receptor antagonist) and emonapride (DA D2 receptor antagonist) are ineffective. In conclusion, 5-HT1A receptors are involved in mediation of isolation-induced aggressive behaviour in mice. The involvement of other 5-HT receptor subtypes needs further clarification. The adrenergic system may also be involved. DA antagonists are ineffective.

Key words

Aggression Isolation-induced Mice Serotonin 5-HT Drug discrimination 

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Copyright information

© Springer-Verlag 1993

Authors and Affiliations

  • Connie Sánchez
    • 1
  • Jørn Arnt
    • 1
  • John Hyttel
    • 1
  • Ejner K. Moltzen
    • 2
  1. 1.Pharmacological ResearchH. Lundbeck A/SValbyDenmark
  2. 2.Department of Medicinal ChemistryH. Lundbeck A/SValbyDenmark

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