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

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-HT_1A 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-HT_1A and-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-HT_1A 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 ( ₁-adrenoceptor antagonist), clonidine ( ₂-adrenoceptor agonist), clenbuterol (-adrenoceptor agonist), ketanserin (5-HT₂ receptor and ₁-adrenoceptor antagonist), clozapine and (–)-octoclothepin (dopamine (DA), 5-HT₂ receptor and ₁-adrenoceptor antagonist) all show an antiaggressive effect. SCH 23390 (DA D₁ receptor antagonist) and emonapride (DA D₂ receptor antagonist) are ineffective. In conclusion, 5-HT_1A 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.