The potential role of dopamine D3 receptor neurotransmission in cognition

Shinichiro Nakajima, Philip Gerretsen, Hiroyoshi Takeuchi, Fernando Caravaggio, Tiffany Chow, Bernard Le Foll, Benoit Mulsant, Bruce Pollock, Ariel Graff-Guerrero

Research output: Contribution to journalReview article

90 Citations (Scopus)

Abstract

Currently available treatments have limited pro-cognitive effects for neuropsychiatric disorders, such as schizophrenia, Parkinson's disease and Alzheimer's disease. The primary objective of this work is to review the literature on the role of dopamine D3 receptors in cognition, and propose dopamine D3 receptor antagonists as possible cognitive enhancers for neuropsychiatric disorders. A literature search was performed to identify animal and human studies on D3 receptors and cognition using PubMed, MEDLINE and EMBASE. The search terms included "dopamine D3 receptor" and "cognition". The literature search identified 164 articles. The results revealed: (1) D3 receptors are associated with cognitive functioning in both healthy individuals and those with neuropsychiatric disorders; (2) D3 receptor blockade appears to enhance while D3 receptor agonism seems to impair cognitive function, including memory, attention, learning, processing speed, social recognition and executive function independent of age; and (3) D3 receptor antagonists may exert their pro-cognitive effect by enhancing the release of acetylcholine in the prefrontal cortex, disinhibiting the activity of dopamine neurons projecting to the nucleus accumbens or prefrontal cortex, or activating CREB signaling in the hippocampus. These findings suggest that D3 receptor blockade may enhance cognitive performance in healthy individuals and treat cognitive dysfunction in individuals with a neuropsychiatric disorder. Clinical trials are needed to confirm these effects.

Original languageEnglish
Pages (from-to)799-813
Number of pages15
JournalEuropean Neuropsychopharmacology
Volume23
Issue number8
DOIs
Publication statusPublished - 2013 Aug

Keywords

  • Cognition
  • Dopamine D3 receptor
  • Dopamine D3 receptor antagonist

ASJC Scopus subject areas

  • Pharmacology
  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Pharmacology (medical)

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  • Cite this

    Nakajima, S., Gerretsen, P., Takeuchi, H., Caravaggio, F., Chow, T., Le Foll, B., Mulsant, B., Pollock, B., & Graff-Guerrero, A. (2013). The potential role of dopamine D3 receptor neurotransmission in cognition. European Neuropsychopharmacology, 23(8), 799-813. https://doi.org/10.1016/j.euroneuro.2013.05.006