Physiological, pathophysiological and therapeutic roles of 5-HT systems in learning and memory

Rev Neurosci. 1998;9(4):275-89. doi: 10.1515/revneuro.1998.9.4.275.


Multiple 5-hydroxytryptamine (5-HT) receptors have been identified (5-HT1A/1B/1D/1E/1F, 5-HT2A/2B/2C, 5-HT3A/3B, 5-HT4A/4B, 5-HT5A/5B, 5-HT6 and 5-HT7A/7B/7C/7D) and extensive evidence suggests that 5-HT receptors have a role in learning and memory. Indeed, available evidence strongly supports physiological, pathophysiological and therapeutic roles of 5-HT systems in cognitive processes, although the evidence seems incomplete. Indeed, there has been a clear tendency to use pre-learning administration most frequently, whereas post-learning and pre-retention administration protocols have been utilized in only a few studies, and probably this trend has led to missed relevant information. For instance, when pre- vs post-training administration of 5-HT1A agonist, 5-HT2 antagonists and 5-HT4 agonists have been compared contrasting findings were reported in aversive and appetitive learning tasks. Emerging evidence also indicates that 5-HT1A and 5-HT4 receptor agonists, as well as, 5-HT1A antagonists, 5-HT2 antagonists, 5-HT3 antagonists and 5-HT uptake inhibitors may have therapeutic utility in the treatment of Alzheimer's disease and amnesia. Inasmuch as the activation or blockade of diverse 5-HT receptors is able to modulate cognitive processes, and 5-HT uptake inhibition could have therapeutic applications in the treatment of cognitive disorders, it seems evident that the role of 5-HT in learning and memory is more complex than a simple imbalance. Consequently, the notion that activation of the 5-HT systems impairs performance, whereas reduced serotonergic function may facilitate learning, must be reconsidered.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Humans
  • Learning Disabilities / drug therapy*
  • Memory Disorders / drug therapy*
  • Serotonin / metabolism
  • Serotonin / physiology*
  • Serotonin Antagonists / therapeutic use*
  • Serotonin Receptor Agonists / therapeutic use*
  • Serotonin Uptake Inhibitors / therapeutic use


  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Serotonin Uptake Inhibitors
  • Serotonin