Psychopharmacology

, Volume 232, Issue 17, pp 3287–3295

Behavioral and neurophysiological effects of Ro 10-5824, a dopamine D4 receptor partial agonist, in common marmosets

  • Shunsuke Nakazawa
  • Takeshi Murai
  • Masanori Miyauchi
  • Manato Kotani
  • Kazuhito Ikeda
Original Investigation

DOI: 10.1007/s00213-015-3978-y

Cite this article as:
Nakazawa, S., Murai, T., Miyauchi, M. et al. Psychopharmacology (2015) 232: 3287. doi:10.1007/s00213-015-3978-y

Abstract

Rationale

Growing evidence suggests that dopamine D4 receptors (D4Rs) are involved in controlling executive functions. We have previously demonstrated that Ro 10-5824, a D4R partial agonist, improves the performance of common marmosets in the object retrieval detour (ORD) task. However, the neural mechanisms underlying this improvement are unknown.

Objectives

We investigated the behavioral and neurophysiological effects of Ro 10-5824 in common marmosets.

Methods

The effects of Ro 10-5824 on cognitive function were evaluated using the ORD task. The neurophysiological effects of Ro 10-5824 were investigated by quantitative electroencephalography, especially on baseline gamma band activity in the frontal cortex. The effects of Ro 10-5824 on spontaneous locomotion were also assessed.

Results

Systemic administration of Ro 10-5824 at 3 mg/kg significantly increased the success rate in the ORD task. At doses of 1 and 3 mg/kg, Ro 10-5824 increased baseline gamma band activity in the frontal cortex. Ro 10-5824 had no effect on spontaneous locomotion.

Conclusions

Activation of D4R by Ro 10-5824 improves the success rate in the ORD task and increases baseline gamma band activity in the frontal cortex without affecting locomotion in common marmosets. These findings highlight the role of D4R in gamma oscillations of non-human primates. As gamma oscillations are thought to be involved in attention and behavioral inhibition, our results suggest D4R agonists may improve these cognitive functions by modulating baseline gamma band activity in the frontal cortex.

Keywords

Non-human primate Dopamine D4 receptor (D4R) Electroencephalography (EEG) Gamma oscillations Object retrieval detour task (ORD task) Cognition Attention deficit hyperactivity disorder (ADHD) 

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Shunsuke Nakazawa
    • 1
  • Takeshi Murai
    • 1
  • Masanori Miyauchi
    • 1
  • Manato Kotani
    • 1
  • Kazuhito Ikeda
    • 1
  1. 1.Drug Development Research LaboratoriesSumitomo Dainippon Pharma Co. LtdOsakaJapan

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