Serotonin/dopamine interaction in learning

Prog Brain Res. 2008;172:567-602. doi: 10.1016/S0079-6123(08)00927-8.


Dopamine (DA)-serotonin interactions dealing with learning and memory functions have been apparent from experimental approaches over the past decade. However, since the former evidence showing that these cerebral neurotransmitter systems are involved in the regulation of the same cognitive processes, few experimental studies have been done to further clarify the nature of DA-serotonin interactions for cognitive processes sharing common brain structures. Nevertheless, a regulatory role of 5-HT/DA interactions in cognition and the prefrontal cortex (PFC) and the striatum as a neuroanatomical substrate for these DA/5-HT interactions, are now recognized. Experimental evidence indicates that pharmacological disruption of serotonin neurotransmission results in a facilitative effect on the processing of mnemonic information by cerebral regions under strong, functional DA modulation, such as the striatum and the PFC; on the other hand, increased serotonin neurotransmission appears to have a detrimental effect on cognitive functions integrated in these structures. These effects seem to occur through the interaction of different pre- and postsynaptic DA and serotonin receptor subtypes acting as opposite systems underlying cognitive abilities. Some studies, focused on DA-serotonin interactions underlying the pathophysiology of neurological and psychiatric diseases, which evolve with cognitive dysfunctions in human beings, have shown that drugs that are able to modify DA or serotonin neurotransmission may exert beneficial effects on cognitive functions, even though improvement of motor, mood and behavioural disturbances are the main objectives of pharmacological treatment of these diseases. The complete significance of DA-serotonin interactions in cognitive functions could be addressed by future experimental and clinical studies.

Publication types

  • Review

MeSH terms

  • Animals
  • Behavior, Animal / physiology
  • Cognition / physiology
  • Corpus Striatum / anatomy & histology
  • Corpus Striatum / physiology
  • Dopamine / metabolism*
  • Dopamine Agents / metabolism
  • Humans
  • Learning / physiology*
  • Memory / physiology
  • Neurons / metabolism
  • Prefrontal Cortex / anatomy & histology
  • Prefrontal Cortex / physiology
  • Protein Isoforms / metabolism
  • Receptors, Dopamine / metabolism
  • Receptors, Serotonin / metabolism
  • Serotonin / metabolism*
  • Serotonin Agents / metabolism
  • Synaptic Transmission / physiology


  • Dopamine Agents
  • Protein Isoforms
  • Receptors, Dopamine
  • Receptors, Serotonin
  • Serotonin Agents
  • Serotonin
  • Dopamine