, Volume 105, Issue 2, pp 162–168 | Cite as

Parametric determinants in pre-stimulus modification of acoustic startle: interaction with ketamine

  • Robert S. Mansbach
  • Mark A. Geyer
Original Investigations


Prepulse inhibition of the acoustic startle response is a form of reflex modification known to be sensitive to drugs and to subtle procedural manipulations. The present study examined the importance of prepulse length and prepulse-pulse interval in the expression of prepulse inhibition and its modification by the noncompetitive N-methyl-d-aspartate antagonist, ketamine. In contrast to a previous report, ketamine disrupted prepulse inhibition at doses of 5.6 and 10 mg/kg when its short time course was taken into consideration. In a second experiment, the amount of prepulse inhibition was found to be directly related to prepulse length, with prepulse inhibition produced by shorter prepulse durations slightly more sensitive to disruption by ketamine. A third experiment examined prepulse-pulse time intervals (30–2000 ms). While prepulse inhibition produced by prepulses occurring 60–500 ms before the startle stimulus was disrupted by 10 mg/kg of ketamine, prepulses preceding the startle stimulus by only 30 ms produced either no effect or slight prepulse facilitation under control conditions, and significant prepulse facilitation when ketamine was administered. A fourth experiment examined the time course of prestimulus modification by continuous lead stimuli, ranging in onset from 15 to 75 ms before the startle stimulus. Prepulse facilitation, when observed, tended to occur in earlier portions of the session and was enhanced by ketamine. These results suggest that prestimulus modification of the startle reflex has important parametric and experiential determinants that may influence the effects of drugs. Some of these temporal determinants may have relevance to sensorimotor function in schizophrenia.

Key words

Prepulse inhibition Ketamine Rat Schizophrenia 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Adler LE, Rose G, Freedman R (1986) Neurophysiological studies of sensory gating in rats: effects of amphetamine, phencyclidine, and haloperidol. Biol Psychiatry 1:787–798CrossRefGoogle Scholar
  2. Blumenthal TD, Gescheider (1987) Modification of the acoustic startle reflex by a tactile prepulse: the effects of stimulus onset asynchrony and prepulse intensity. Psychophysiology 24:320–327PubMedGoogle Scholar
  3. Blumenthal TD, Levey BJ (1989) Prepulse rise time and startle reflex modification: different effects for discrete and continuous prepulses. Psychophysiology 26:158–165PubMedGoogle Scholar
  4. Bowery NG, Wong EHF, Hudson AL (1988) Quantitative autoradiography of [3H]-MK-801 binding sites in mammalian brain. Br J Pharmacol 93:944–954PubMedGoogle Scholar
  5. Braff DL, Stone C, Callaway E, Geyer MA, Glick ID, Bali L (1978) Prestimulus effects on human startle reflex in normals and schizophrenics. Psychophysiology 15:339–343PubMedGoogle Scholar
  6. Crofton KM, Dean KF, Sheets LP, Peele DB (1991) Evidence for an involvement of associative conditioning in reflex modification of the acoustic startle response with gaps in background noise. Psychobiology (in press)Google Scholar
  7. Davis M, Mansbach RS, Swerdlow NR, Campeau S, Braff DL, Geyer MA (1990) Apomorphine disrupts the inhibition of acoustic startle induced by weak prepulses in rats. Psychopharmacology 102:1–4PubMedGoogle Scholar
  8. Dykman BM, Ison JR (1979) Temporal integration of acoustic stimulation obtained in reflex inhibition in rats and humans. J Comp Physiol Psychol 93:939–945PubMedGoogle Scholar
  9. Geyer MA, Braff DL, Mansbach RS (1989) Failure of haloperidol to block the disruption of sensory motor gating induced by phencyclidine and MK801. Biol Psychiatry 25:169A-170ACrossRefGoogle Scholar
  10. Graham FK (1975) The more or less startling effects of weak prestimuli. Psychophysiology 12:238–248PubMedGoogle Scholar
  11. Graham FK and Murray GM (1977) Discordant effects of weak prestimulation on magnitude and latency of the reflex blink. Physiol Psychol 5:108–114Google Scholar
  12. Hoffman HS, Ison JR (1980) Reflex modification in the domain of startle: I. Some empirical findings and their implications for how the nervous system processes sensory input. Psychol Rev 87:175–189CrossRefPubMedGoogle Scholar
  13. Hubner CB, Pert A (1990) Phencyclidine, but not MK-801, produces increases in extracellular dopamine levels as assessed by in vivo microdialysis. Soc Neurosci Abstr 16:583Google Scholar
  14. Ison JR, Hammond GR (1971) Modification of the startle reflex in the rat by changes in the auditory and visual environments. J Comp Physiol Psychol 75:435–452PubMedGoogle Scholar
  15. Ison JR, Hammond GR, Krauter EE (1973) Effects of experience on stimulus-produced reflex inhibition in the rat. J Comp Physiol Psychol 83:324–336PubMedGoogle Scholar
  16. Krauter E (1987) Reflex modification of the human auditory startle blink by antecedent interruption of a visual stimulus. Percept Mot Skill 64:727–738Google Scholar
  17. Mansbach RS, Geyer MA (1989) Effects of phencyclidine and phencyclidine biologs on sensorimotor gating in the rat. Neuropsychopharmacology 2:299–308CrossRefPubMedGoogle Scholar
  18. Mansbach RS, Geyer MA, Braff DL (1988) Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507–514PubMedGoogle Scholar
  19. Mansbach RS, Braff DL, Geyer MA (1989) Prepulse inhibition of the acoustic startle response is disrupted by N-ethyl-3,4-methylenedioxyamphetamine (MDEA) in the rat. Eur J Pharmacol 167:49–55CrossRefPubMedGoogle Scholar
  20. Maragos WF, Penny JB, Young AB (1988) Anatomic correlation of NMDA and3H-TCP-labeled receptors in rat brain. J Neurosci 8:493–501PubMedGoogle Scholar
  21. McGhie A, Chapman J (1961) Disorders of attention and perception in early schizophrenia. Br J Med Psychol 34:103–116PubMedGoogle Scholar
  22. Peng R, Mansbach RS, Braff DL, Geyer MA (1990) A D2 dopamine receptor agonist disrupts sensorimotor gating in rats: implications for dopaminergic abnormalities in schizophrenia. Neuropsychopharmacology 3:211–218PubMedGoogle Scholar
  23. Swerdlow NR, Braff DL, Geyer MA (1990) GABAergic projection from nucleus accumbens to ventral pallidum mediates dopamine-induced sensorimotor gating deficits of acoustic startle in rats. Brain Res 532:146–150CrossRefPubMedGoogle Scholar
  24. Winer BJ (1971) Statistical principles in experimental design. McGraw-Hill, New YorkGoogle Scholar
  25. Wong EHF, Kemp JA, Priestley T, Knight AR, Woodruff GN, Iversen LL (1986) The anticonvulsant MK-801 is a potentN-methyl-d-aspartate antagonist. Proc Natl Acad Sci USA 83:7104–7108PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1991

Authors and Affiliations

  • Robert S. Mansbach
    • 1
  • Mark A. Geyer
    • 2
  1. 1.Department of Pharmacology and Toxicologsy, Box 613 MCV Station, Medical College of VirginiaVirginia Commonwealth UniversityRichmondUSA
  2. 2.Department of Psychiatry 0804University of California at San DiegoLa JollaUSA

Personalised recommendations