The effects of dizocilpine and phencyclidine on prepulse inhibition of the acoustic startle reflex and on prepulse-elicited reactivity in C57BL6 mice

Kay Yan Benjamin Yee, D. L Tilly Chang, Joram Feldon

Research output: Journal article publicationJournal articleAcademic researchpeer-review

74 Citations (Scopus)

Abstract

Prepulse inhibition (PPI) of the acoustic startle response refers to the reduction in startle reaction to a startle-eliciting stimulus when it is shortly preceded by a subthreshold prepulse stimulus. Here, we evaluated the possible effects on prepulse-elidted reactivity by dizocilpine (MK-801) and phencyclidine (PCP) in the PPI of acoustic startle paradigm in C57BL6/J mice. The aim was to ascertain whether these two drugs would affect prepulse-elicited reactivity in a manner similar to apomorphine, which enhances prepulse-elicited reactivity at doses that disrupt PPI. In two dose-response studies, we showed that both drugs exhibited a tendency to attenuate prepulse-elicited reaction at higher doses when PPI was severely disrupted. On the other hand, at lower doses when PPI was marginally disrupted, reaction to the prepulse, if anything, tended to increase. It is concluded that PPI disruption induced by noncompetitive NMDA receptor antagonists can be distinguished from apomorphine-induced PPI disruption by their concomitant effects on prepulse-elicited reactivity. Our data support the suggestion that dopamine receptor agonists and NMDA receptor antagonists disrupt PPI via interference with distinct neural pathways or neuronal systems.
Original languageEnglish
Pages (from-to)1865-1877
Number of pages13
JournalNeuropsychopharmacology
Volume29
Issue number10
DOIs
Publication statusPublished - 1 Oct 2004
Externally publishedYes

Keywords

  • MK-801
  • NMDA antagonist
  • PCP
  • PPI
  • Schizophrenia
  • Sensorimotor gating

ASJC Scopus subject areas

  • Pharmacology

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