Psychopharmacology

, Volume 207, Issue 4, pp 571–581

Impact of dopamine–glutamate interactions on striatal neuronal nitric oxide synthase activity

  • Kristina E. Hoque
  • Raksha P. Indorkar
  • Stephen Sammut
  • Anthony R. West
Original Investigation

DOI: 10.1007/s00213-009-1687-0

Cite this article as:
Hoque, K.E., Indorkar, R.P., Sammut, S. et al. Psychopharmacology (2010) 207: 571. doi:10.1007/s00213-009-1687-0

Abstract

Rationale

It is known that dopamine (DA) D1 receptor activation stimulates striatal nitric oxide (NO) synthesis, whereas D2 receptor activation produces the opposite effect. However, the mechanisms involved in the dopaminergic modulation of nitric oxide synthase (NOS) are unknown.

Objectives

We hypothesized that the effects of DA on striatal NO signaling are dependent on ongoing glutamatergic activation of NOS. Therefore, the current study examined whether intact N-methyl-d-aspartic acid (NMDA) receptor activation is required for the dopaminergic modulation of NOS activity.

Methods

We assessed the impact of pharmacological manipulations of D1, D2, and NMDA receptors on NOS activity in the dorsal striatum and motor cortex using nicotinamide adenine dinucleotide phosphate-diaphorase (NADPH-d) histochemistry. Drugs were administered systemically to conscious animals and NADPH-d staining was quantified in these regions using ex vivo measurements of tissue optical density.

Results

Administration of the neuronal NOS inhibitor NG-propyl-l-arginine (NPA), the D1 receptor antagonist SCH 23390, and the NMDA receptor antagonist 3-phosphonopropyl-piperazine-2-carboxylic acid (CPP) all attenuated staining selectively in the striatum. Administration of the D2 receptor agonist quinpirole decreased NADPH-d staining in both the striatum and cortex. Striatal NADPH-d staining elicited by administration of the D1 receptor agonist SKF 81297 or the D2 receptor antagonist eticlopride was attenuated by NPA, SCH 23390, and CPP pretreatment. Quinpirole pretreatment also abolished the facilitatory effect of SKF 81297.

Conclusions

These studies show for the first time that ongoing NMDA receptor activation is necessary for the modulation of striatal NOS activity by both facilitatory (D1 receptor activation) and inhibitory (D2 receptor activation) dopaminergic signaling mechanisms.

Keywords

Dopamine Nitric oxide Nitric oxide synthase NMDA receptor Striatum Cortex 

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Kristina E. Hoque
    • 1
  • Raksha P. Indorkar
    • 1
  • Stephen Sammut
    • 1
  • Anthony R. West
    • 1
  1. 1.Department of NeuroscienceThe Chicago Medical School at Rosalind Franklin University of Medicine and ScienceNorth ChicagoUSA

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