Postsynaptic 5-HT1 receptors and offensive aggression in rats: a combined behavioural and autoradiographic study with eltoprazine

Pharmacol Biochem Behav. 1991 Feb;38(2):447-58. doi: 10.1016/0091-3057(91)90305-l.


The present study was designed to assess whether the antiaggressive effects of eltoprazine are mediated via presynaptic and/or postsynaptic 5-HT1 receptors. We describe the effects of central 5-HT depletion 1) on the behaviour of resident TMD-S3 rats in a territorial situation, 2) on the efficacy of eltoprazine to inhibit offensive aggression, and 3) on the 5-HT1A, 5-HT1B and 5-HT1C receptor binding in brains of rats previously used in behavioural studies. Male resident rats were given combined 5,7-dihydroxytryptamine (5,7-DHT) injections into the dorsal and median raphe nuclei. Two to four weeks after the lesions, rats were confronted with an intruder Wiser rat in their home cage for a 10-min period. The 5,7-DHT treatment resulted in a modest reduction of offensive behaviour, while having no effects on other social and nonsocial behaviours. Oral administration of eltoprazine (1 mg/kg) specifically reduced offensive aggression in both sham- and 5,7-DHT-lesioned animals, leaving social interest and exploration intact or even increasing it. A low dose (0.3 mg/kg) of eltoprazine did not affect the behavioural repertoire of sham-operated rats, whereas this dose significantly reduced offense behaviours in the 5,7-DHT-lesioned residents. Quantitative autoradiographic studies 5 weeks after 5,7-DHT treatment revealed a significant increase in radioligand binding to 5-HT1A, 5-HT1B and 5-HT1C sites in many brain regions studied, except for the raphe nuclei where [3H]8-OH-DPAT binding to 5-HT1A sites was markedly reduced. The concentrations of 5-HT and 5-HIAA in frontal cortex were reduced to approximately 10% of controls. The results indicate that serotonin has a stimulatory rather than an inhibitory influence on offensive aggressive behaviour. Central 5-HT depletion does not prevent the antiaggressive effects of eltoprazine, indicating a role for postsynaptic 5-HT1 receptors in the modulation of offensive aggression. The 5,7-DHT-induced overall upregulation of 5-HT1A, 5-HT1B and 5-HT1C binding sites suggests that these three receptor subtypes receive a tonic serotonergic influence. It is conceivable that this postsynaptic 5-HT1 receptor supersensitivity is reflected by the increased efficacy of eltoprazine to inhibit offensive aggression.

MeSH terms

  • 5,7-Dihydroxytryptamine / pharmacology
  • 8-Hydroxy-2-(di-n-propylamino)tetralin
  • Aggression / drug effects*
  • Animals
  • Autoradiography
  • Biogenic Monoamines / metabolism
  • Brain / anatomy & histology
  • Male
  • Piperazines / pharmacology*
  • Rats
  • Rats, Inbred Strains
  • Receptors, Serotonin / drug effects
  • Receptors, Serotonin / physiology*
  • Serotonin / physiology
  • Serotonin Antagonists / pharmacology
  • Synapses / drug effects
  • Synapses / physiology*
  • Tetrahydronaphthalenes / pharmacology


  • Biogenic Monoamines
  • Piperazines
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Tetrahydronaphthalenes
  • 5,7-Dihydroxytryptamine
  • Serotonin
  • eltoprazine
  • 8-Hydroxy-2-(di-n-propylamino)tetralin