Nitric oxide synthase inhibitors attenuate phencyclidine-induced disruption of prepulse inhibition.

Glutamate stimulation of N-methyl-D-aspartate (NMDA) receptors results in release of nitric oxide which may mediate the effects of NMDA receptor stimulation and/or may result in feedback inhibition of the presynaptic neuron. Results of a previous study showed that nitric oxide synthase (NOS) inhibitors blocked dizocilpine-induced behavior in mice. In the present study, NOS inhibitors were tested in combination with phencyclidine (PCP), a drug which typically dose-dependently disrupts prepulse inhibition of the acoustic startle response in rats. Alone, NOS inhibitors and promoters do not affect prepulse inhibition; however, when tested in combination with PCP, the NOS inhibitors, L-NOARG, 7-nitroindazole and arcaine--but not the NR2B-selective polyamine site NMDA antagonist, eliprodil--attenuated PCP-induced disruption of prepulse inhibition of the acoustic startle response. These effects are similar to those produced by many atypical antipsychotics and suggests that this class of drugs should be investigated further for their potential utility as antipsychotics and as treatments for PCP abuse.
AuthorsJ L Wiley
JournalNeuropsychopharmacology : official publication of the American College of Neuropsychopharmacology (Neuropsychopharmacology) Vol. 19 Issue 1 Pg. 86-94 (Jul 1998) ISSN: 0893-133X [Print] UNITED STATES
PMID9608580 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • Biguanides
  • Biogenic Polyamines
  • Enzyme Inhibitors
  • Excitatory Amino Acid Antagonists
  • Indazoles
  • Piperidines
  • Receptors, N-Methyl-D-Aspartate
  • Nitroarginine
  • 7-nitroindazole
  • arcaine
  • Nitric Oxide Synthase
  • Phencyclidine
  • eliprodil
  • Acoustic Stimulation
  • Animals
  • Biguanides (pharmacology)
  • Biogenic Polyamines (metabolism)
  • Enzyme Inhibitors (pharmacology)
  • Excitatory Amino Acid Antagonists (pharmacology)
  • Indazoles (pharmacology)
  • Inhibition (Psychology)
  • Male
  • Nitric Oxide Synthase (antagonists & inhibitors)
  • Nitroarginine (pharmacology)
  • Phencyclidine (pharmacology)
  • Piperidines (pharmacology)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, N-Methyl-D-Aspartate (drug effects, metabolism)
  • Reflex, Startle (drug effects)

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