Interactions between 5-hydroxytryptamine receptor subtypes: is a disturbed receptor balance contributing to the symptomatology of depression in humans?

Pharmacol Ther. 1995 Apr;66(1):17-37. doi: 10.1016/0163-7258(94)00075-e.


The purpose of this review is to describe the consequences of antidepressant treatment on the behaviour of rodents after activation of serotonin (5-hydroxytryptamine, 5-HT) receptor subtypes. In a summary table, the involvement of 5-HT receptors in inducing behavioural changes are described. It is emphasized that these effects are not always only exclusively linked to serotonergic functions nor that they are only initiated by central 5-HT receptors. Hereafter, the complex mutual inhibitory effects of 5-HT receptor subtype-mediated processes are discussed by interpreting effects of antagonists and describing the different effects of low and high doses of mixed 5-HT1C/5-HT2 receptor agonists. Mutual influences are seen particularly with 5-HT1A, 5-HT1C and 5-HT2, but not with 5-HT1B, 5-HT1D or 5-HT3 receptor-mediated effects. It is shown that the behavioural consequences of 5-HT1A, 5-HT1C and 5-HT2 receptor stimulation may be changed by brain lesions or chronic treatment with drugs. Among these drugs are the antidepressants. Finally, 5-HT receptor function in depressed patients is discussed, and the hypothesis is proposed that an important function of antidepressants is to restore a disturbed balance between 5-HT1A, 5-HT1C and 5-HT2 receptors in depressed patients.

Publication types

  • Review

MeSH terms

  • Animals
  • Antidepressive Agents / administration & dosage
  • Antidepressive Agents / pharmacology*
  • Antidepressive Agents / therapeutic use
  • Behavior, Animal / drug effects*
  • Blood-Brain Barrier / drug effects
  • Depression / drug therapy
  • Depression / etiology*
  • Disease Models, Animal
  • Drug Interactions
  • Humans
  • Rats
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / drug effects*
  • Receptors, Serotonin / physiology
  • Selective Serotonin Reuptake Inhibitors / administration & dosage
  • Selective Serotonin Reuptake Inhibitors / pharmacology
  • Selective Serotonin Reuptake Inhibitors / therapeutic use
  • Serotonin Receptor Agonists / administration & dosage
  • Serotonin Receptor Agonists / pharmacology
  • Serotonin Receptor Agonists / therapeutic use


  • Antidepressive Agents
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors