The role of serotonergic mechanisms in inhibition of isolation-induced aggression in male mice |
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Authors: | Connie Sánchez Jørn Arnt John Hyttel Ejner K Moltzen |
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Institution: | (1) Pharmacological Research, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark;(2) Department of Medicinal Chemistry, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark |
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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 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-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 (
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-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. |
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Keywords: | Aggression Isolation-induced Mice Serotonin 5-HT Drug discrimination |
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