Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635

Behav Pharmacol. 1997 Nov;8(6-7):585-606. doi: 10.1097/00008877-199711000-00016.


Acute and chronic antidepressant drug treatments respectively decrease and increase the aggressive behaviour of resident rats during encounters with unfamiliar conspecifics. We have now examined the effect of the 5-hydroxytryptamine1A receptor antagonist, WAY-100635, on fluoxetine-, paroxetine- or venlafaxine-induced changes in aggression. WAY-100635 (0.1 mg/kg), which did not modify behaviour when given alone, potentiated the venlafaxine (5.54 mg/kg)-induced reduction in aggression after acute treatment and, during chronic treatment, accelerated the fluoxetine (0.34 mg/kg/day)-induced increase in aggression, from day 5 to day 2. A similar change in time course was seen with paroxetine (0.33 mg/kg/day), although the increase in aggression was smaller. Venlafaxine (5.54 mg/kg/day, alone or co-administered with WAY-100635) increased aggression by day 2. During chronic treatment, therefore, venlafaxine, at the dose used, had a more rapid onset of action than either fluoxetine or paroxetine, whereas the fluoxetine- and paroxetine-, but not the venlafaxine-, induced increase in aggression was accelerated by WAY-100635. These studies further support the hypothesis that selective blockade of the 5-hydroxytryptamine1A receptor augments the effects of antidepressant drugs in an animal model predictive of antidepressant activity, presumably by concomitant blockade of the somatodendritic 5-hydroxytryptamine1A autoreceptor-mediated negative feedback system of serotonergic neurones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Agonistic Behavior / drug effects*
  • Animals
  • Anti-Anxiety Agents / pharmacology
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents, Second-Generation / pharmacology
  • Benzodiazepines
  • Central Nervous System Depressants / pharmacology
  • Cyclohexanols / pharmacology
  • Drug Implants
  • Drug Synergism
  • Ethanol / pharmacology
  • Fluoxetine / pharmacology
  • Interpersonal Relations
  • Male
  • Piperazines / administration & dosage
  • Piperazines / pharmacology*
  • Pyridines / administration & dosage
  • Pyridines / pharmacology*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists / administration & dosage
  • Serotonin Antagonists / pharmacology*
  • Time Factors
  • Venlafaxine Hydrochloride


  • Anti-Anxiety Agents
  • Antidepressive Agents
  • Antidepressive Agents, Second-Generation
  • Central Nervous System Depressants
  • Cyclohexanols
  • Drug Implants
  • Piperazines
  • Pyridines
  • Receptors, Serotonin
  • Receptors, Serotonin, 5-HT1
  • Serotonin Antagonists
  • Fluoxetine
  • Benzodiazepines
  • Ethanol
  • N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide
  • Venlafaxine Hydrochloride