Psychopharmacology

, Volume 142, Issue 1, pp 78–84

Dopamine D4 receptor antagonist reversal of subchronic phencyclidine-induced object retrieval/detour deficits in monkeys

  • J. D. Jentsch
  • Jane R. Taylor
  • D. Eugene Redmond Jr
  • John D. Elsworth
  • Kenneth D. Youngren
  • Robert H. Roth
ORIGINAL INVESTIGATION

DOI: 10.1007/s002130050865

Cite this article as:
Jentsch, J., Taylor, J., Redmond Jr, D. et al. Psychopharmacology (1999) 142: 78. doi:10.1007/s002130050865
  • 120 Downloads

Abstract

D4 dopamine receptors (DRs) are enriched in the primate prefrontal cortex, a brain region implicated in cognitive processes, and mesoprefrontal dopaminergic systems appear to be involved in modulating some cognitive functions of the prefrontal cortex. Despite anatomical localization of D4 DRs within the frontal cortex, the role of these receptors, specifically, in the regulation of cognition or behavior in primates is unknown. In these studies, we sought to learn whether specific antagonism of D4 DRs would affect performance of a task dependent on the frontostriatal system. The effects of NGD94-1 (2-phenyl-4(5)-[4-(2-pyrimidinyl)-piperazin-1-yl)-methyl]-imidazole dimaleate), a potent and selective D4 DR antagonist and haloperidol, a non-specific D2-like DR antagonist, on the performance of an object retrieval/detour task by monkeys were examined. The effects of these antagonists on the object retrieval task were evaluated in normal control monkeys and in subjects repeatedly exposed to phencyclidine (PCP), to induce frontal cortical dopaminergic and cognitive dysfunction. NGD94-1 (1–5 mg/kg) reversed the cognitive deficits of PCP pre-treated monkeys, whereas haloperidol (25 μg/kg) exacerbated PCP-induced performance impairments. A low dose of NGD94-1 failed to affect performance of control subjects, while both haloperidol and a high dose of NGD94-1 impaired control performance. These data show, for the first time, that D4 DRs modulate the cognitive functions of the frontostriatal system.

Key words Prefrontal cortex Psychotomimetic Memory Dopamine Primate D4 receptor 

Copyright information

© Springer-Verlag Berlin Heidelberg 1999

Authors and Affiliations

  • J. D. Jentsch
    • 1
  • Jane R. Taylor
    • 2
  • D. Eugene Redmond Jr
    • 2
  • John D. Elsworth
    • 3
  • Kenneth D. Youngren
    • 5
  • Robert H. Roth
    • 3
  1. 1.Section of Neurobiology, Yale University School of Medicine, P.O. Box 208001, New Haven, CT 06520-8001, USAUS
  2. 2.Department of Psychiatry, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USAUS
  3. 3.Department of Neurosurgery, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USAUS
  4. 4.Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USAUS
  5. 5.International Neuroscience Program, Yale University School of Medicine, 333 Cedar Street, New Haven, CT 06510, USAUS

Personalised recommendations