Phencyclidine and auditory sensory gating in the hippocampus of the rat

Christine L. Miller, Paula C. Bickford, Vera Luntz-Leybman, L. E. Adler, G. A. Gerhardt, R. Freedman

Research output: Contribution to journalArticlepeer-review

57 Scopus citations


The psychotomimetic drug 1-(1-phenylcyclohexyl) piperidine (PCP, phencyclidine) was found to cause a deficit in the gating of the response of the hippocampal neuron to repeated auditory stimuli, which is similar to a particular physiological feature observed in human psychosis. Other drugs, with sigma agonist and/or N-methyl-D-aspartate (NMDA) antagonist effects, were administered and their ability to cause a loss of auditory gating was compared to that of PCP. The rank order of effectiveness was levoxodrol > PCP and (+)-5-methyl-10,11-dihydro-5H-dibenzo(a,d)cyclohepten-5,10-imine maleate (MK-801) > N-allylnormetazocine (SKF 10047) > dexoxodrol > 3-(±)2-carboxypiperazine-4-yl) propyl-1-phosphonate (CPP). Further studies of two of the drugs, PCP and MK-801, showed that selective lesioning of the noradrenergic input with the neurotoxin DSP4, as well as less selective depletion of monoamines with reserpine, blocked the loss of gating. Phencyclidine, and other drugs with the same spectrum of action, most likely disrupt gating by increasing noradrenergic activity through a sigma mechanism.

Original languageEnglish
Pages (from-to)1041-1048
Number of pages8
Issue number10
StatePublished - Oct 1992

Bibliographical note

Funding Information:
Acknowledgements--This work was supported by the Veterans Administration Medical Research Service, by DA-02429, MH-38321, MH-44212 and a grant to Christine L. Miller from the Stanley Foundation.


  • NMDA
  • auditory gating
  • norepinephrine
  • phencyclidine
  • sigma receptors

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience


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