Psychopharmacology

, Volume 183, Issue 4, pp 439–445

Phosphodiesterase inhibition by sildenafil citrate attenuates a maze learning impairment in rats induced by nitric oxide synthase inhibition

  • Bryan D. Devan
  • Jonna L. Bowker
  • Kara B. Duffy
  • Ila S. Bharati
  • Mariana Jimenez
  • Demetrio Sierra-MercadoJr.
  • Christopher M. Nelson
  • Edward L. Spangler
  • Donald K. Ingram
Original Investigation

DOI: 10.1007/s00213-005-0232-z

Cite this article as:
Devan, B.D., Bowker, J.L., Duffy, K.B. et al. Psychopharmacology (2006) 183: 439. doi:10.1007/s00213-005-0232-z

Abstract

Rationale

The nitric oxide (NO)–cyclic guanosine monophosphate (cGMP) signal transduction pathway has been implicated in some forms of learning and memory. Recent findings suggest that inhibition of phosphodiesterase (PDE) enzymes that degrade cGMP may have memory-enhancing effects.

Objectives

We examined whether treatment with sildenafil citrate, a PDE type 5 inhibitor, would attenuate a learning impairment induced by inhibition of NO synthase [60 mg/kg Nω-nitro-l-arginine methyl ester (l-NAME), i.p.].

Methods

Rats were pretrained in a one-way active avoidance of foot shock in a straight runway and, on the next day, received 15 training trials in a 14-unit T-maze, a task that has been shown to be sensitive to aging and impairment of central NO signaling systems. Combined treatments of l-NAME or saline and sildenafil (1.0, 1.5, 3.0, or 4.5 mg/kg, i.p.) or vehicle were given 30 and 15 min before training, respectively. Behavioral measures of performance included entries into incorrect maze sections (errors), run time from start to goal (latency), shock frequency, and shock duration.

Results

Statistical analysis revealed that l-NAME impaired maze performance and that sildenafil (1.5 mg/kg) significantly attenuated this impairment. Control experiments revealed that administration of l-NAME alone did not significantly increase latencies in a one-way active avoidance test and that different doses of sildenafil alone did not significantly alter complex maze performance.

Conclusions

The results indicate that sildenafil may improve learning by modulating NO–cGMP signal transduction, a pathway implicated in age-related cognitive decline and neurodegenerative disease.

Keywords

Phosphodiesterase inhibition Nitric oxide Nitric oxide synthase Cyclic GMP NMDA receptor activation Aging Animal model Neurodegenerative disease Learning and memory Cognitive performance 

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  • Bryan D. Devan
    • 1
  • Jonna L. Bowker
    • 1
  • Kara B. Duffy
    • 1
  • Ila S. Bharati
    • 1
  • Mariana Jimenez
    • 1
  • Demetrio Sierra-MercadoJr.
    • 1
  • Christopher M. Nelson
    • 1
  • Edward L. Spangler
    • 1
  • Donald K. Ingram
    • 1
  1. 1.Behavioral Neuroscience Section, Laboratory of Experimental Gerontology, Gerontology Research CenterNational Institute on Aging, National Institutes of HealthBaltimoreUSA

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