Potentiation of the time-dependent, antidepressant-induced changes in the agonistic behaviour of resident rats by the 5-HT1A receptor antagonist, WAY-100635.
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.
Mitchell
P J
PJ
School of Pharmacy and Pharmacology, University of Bath, UK.
Redfern
P H
PH
D000378:Agonistic Behavior / Q000187:drug effects*; D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001569:Benzodiazepines; D002492:Central Nervous System Depressants / Q000494:pharmacology; D003511:Cyclohexanols / Q000494:pharmacology; D004343:Drug Implants; D004357:Drug Synergism; D000431:Ethanol / Q000494:pharmacology; D005473:Fluoxetine / Q000494:pharmacology; D007398:Interpersonal Relations; D008297:Male; D010879:Piperazines / Q000008:administration & dosage / Q000494:pharmacology*; D011725:Pyridines / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000008:administration & dosage / Q000494:pharmacology*; D013997:Time Factors; D000069470:Venlafaxine Hydrochloride
D014151:Anti-Anxiety Agents; D000928:Antidepressive Agents; D018687:Antidepressive Agents, Second-Generation; D002492:Central Nervous System Depressants; D003511:Cyclohexanols; D004343:Drug Implants; D010879:Piperazines; D011725:Pyridines; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D005473:Fluoxetine; D001569:Benzodiazepines; D000431:Ethanol; C090413:N-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-N-(2-pyridinyl)cyclohexanecarboxamide; D000069470:Venlafaxine Hydrochloride