Somatodendritic 5-HT(1A) autoreceptors mediate the anti-aggressive actions of 5-HT(1A) receptor agonists in rats: an ethopharmacological study with S-15535, alnespirone, and WAY-100635
| Autor: | Monique Lesourd, Sietse F. de Boer, Elisabeth Mocaer, Jaap M. Koolhaas |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
Male
S-15535 Pyridines Piperazines Body Temperature chemistry.chemical_compound 5HT-(1A) ANTAGONISTS Postsynaptic potential polycyclic compounds heterocyclic compounds rat IN-VIVO SEROTONIN RECEPTORS Chemistry musculoskeletal neural and ocular physiology resident-intruder ELTOPRAZINE serotonin Serotonin Receptor Agonists Aggression Psychiatry and Mental health 8-OH-DPAT Competitive antagonist 5-HT1A receptor Serotonin Antagonists hypothermia BEHAVIOR Agonist medicine.medical_specialty medicine.drug_class Neurotransmission Motor Activity Inhibitory postsynaptic potential BUSPIRONE Internal medicine medicine Alnespirone Animals Spiro Compounds IPSAPIRONE Pharmacology Dose-Response Relationship Drug ANTIDEPRESSANT Rats MICE Endocrinology nervous system Receptors Serotonin Receptors Serotonin 5-HT1 |
| Zdroj: | Neuropsychopharmacology, 23(1), 20-33. Nature Publishing Group |
| ISSN: | 0893-133X |
| Popis: | To elucidate the relative contribution of somatodendritic 5-HT1A autoreceptors and postsynaptic 5-HT1A receptor the specific anti-aggressive properties of 5-HT1A receptor agonists, the influence of the novel benzodioxopiperazine compound S-15535, which behaves in vivo as a competitive antagonist at postsynaptic 5-HT1A receptors and as an agonist at 5-HT1A autoreceptors, upon offensive and defensive aggression was investigated in wild-type rats using a resident-intruder paradigm. S-15535 exerted a potent dose-dependent decrease in offensive, but not defensive, aggressive behavior (inhibitory dose (ID)(50) = 1.11 mg/kg). This anti-aggressive profile was roughly similar to that of the potent pre- and postsynaptic 5-HT1A full agonist alnespirone (ID50 = 1.24). The drug's profound anti-aggressive actions were not accompanied by sedative side effects or signs of the "5HT-(1A) receptor-mediated behavioral syndrome," which are characteristically induced by prototypical 5-HT1A receptor agonists like 8-OH-DPAT and buspirone. The selective pre- and postsynaptic 5-HT1A antagonist WAY-100635, which was inactive given alone, abolished the anti-aggressive effects of S-15535 and alnespirone, thereby confirming the involvement of 5-HT1A receptors. Furthermore, combined administration of S-15535 and alnespirone elicited an additive anti-aggressive effect, providing further support for somatodendritic 5-HT1A receptor involvement. Finally, the postsynaptic 5-HT1A antagonistic properties of S-15535 were confirmed by showing blockade of the alnespirone-induced hypothermia, a postsynaptic 5-HT1A mediated response in the rat. These data provide extensive evidence that the anti-aggressive effects of 5-HT1A receptor agonists are expressed via their action on somatodendritic 5-HT1A autoreceptors, thereby most likely attenuating intruder-activated serotonergic neurotransmission. [Neuropsychopharmacology 23:20-33, 2000] (C) 2000 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. All rights reserved. |
| Databáze: | OpenAIRE |
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