Measurement of Startle Response, Prepulse Inhibition, and Habituation

Mark A. Geyer1, Neal R. Swerdlow1

1 University of California, San Diego, La Jolla, California
Publication Name:  Current Protocols in Neuroscience
Unit Number:  Unit 8.7
DOI:  10.1002/0471142301.ns0807s03
Online Posting Date:  May, 2001
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The startle response is comprised of a constellation of reflexes elicited by sudden, relatively intense stimuli. The startle reflex is useful for studying fundamental properties of nervous function ranging from neurophysiological and anatomical relationships within the pons and reticular formation to forebrain regulation of complex behavioral states and cognitive processes. This unit presents protocols for measurement of the startle response in rats to acoustic stimuli, along with modifications encompassing an experimental manipulation such as drug treatment and measures of habituation of startle; a method for measuring prepulse inhibition (PPI) of startle; and specialized rat handling and calming techniques that supplement the startle protocols.

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Table of Contents

  • Strategic Planning
  • Basic Protocol 1: Basic Test of Acoustic Startle Reactivity
  • Alternate Protocol 1: Between‐Subjects Tests of Startle Reactivity
  • Alternate Protocol 2: Between‐Subjects Tests of Startle Habituation
  • Basic Protocol 2: Testing Prepulse Inhibition (PPI) of Startle
  • Support Protocol 1: Rat Handling
  • Commentary
  • Figures
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Basic Protocol 1: Basic Test of Acoustic Startle Reactivity

  • Forty naive male Sprague‐Dawley rats weighing 250 to 300 g
  • Drugs and placebos
  • Sound‐attenuated testing room
  • SR‐LAB startle apparatus with digitized electronic signal output (San Diego Instruments) or equivalent
  • Calibrated sound level meter (Quest)
  • Drug delivery system

Alternate Protocol 1: Between‐Subjects Tests of Startle Reactivity

  • Apomorphine⋅HCl for the administration of 0.1, 0.3, and 1.0 mg/kg injections at a volume of 1.0 ml/kg, prepared fresh
  • Vehicle solution of sterile isotonic saline containing 0.1 mg/ml ascorbic acid, purged of oxygen by sparging with nitrogen gas for 10 min, prepared fresh
  • Sterile 1‐cc syringes
  • Sterile 25‐G syringe needles
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Literature Cited

Literature Cited
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   Braff, D.L., Swerdlow, N.R., and Geyer, M.A. 1995. Gating and habituation deficits in the schizophrenia disorders. Clin. Neurosci. 95:131‐139.
   Cadenhead, K.S., Geyer, M.A., and Braff, D.L. 1993. Impaired startle prepulse inhibition and habituation in schizotypal patients. Am. J. Psychiatry 150:1862‐1867.
   Cassella, J.V. and Davis, M. 1986. The design and calibration of a startle measurement system. Physiol. Behav. 36:377‐383.
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   Dulawa, S.C. and Geyer, M.A. 1996. Psychopharmacology of prepulse inhibition in mice. Chin. J. Physiol. 39:139‐146.
   Ellenbroek, B.A., Geyer, M.A., and Cools, M.A. 1995. The behavior of APO‐SUS rats in animal models with construct validity for schizophrenia. J. Neurosci. 15:7604‐7611.
   Geyer, M.A. and Braff, D.L. 1982. Habituation of the blink reflex in normals and schizophrenic patients. Psychophysiology 19:1‐6.
   Geyer, M.A. and Braff, D.L. 1987. Startle habituation and sensorimotor gating in schizophrenia and related animal models. Schizophr. Bull. 13:643‐668.
   Geyer, M.A. and Tapson, G.S. 1988. Habituation of tactile startle is altered by drugs acting on serotonin‐2 receptors. Neuropsychopharmacology 1:135‐147.
   Geyer, M.A., Swerdlow, N.R., Mansbach, R.S., and Braff, D.L. 1990. Startle response models of sensorimotor gating and habituation deficits in schizophrenia. Brain Res. Bull. 25:485‐498.
   Geyer, M.A., Wilkinson, L.S., Humby, T., and Robbins, T.W. 1993. Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia. Biol. Psychiatry 34:361‐372.
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   Hoffman, H.S. and Searle, J.L. 1968. Acoustic and temporal factors in the evocation of startle. J. Acoust. Soc. Am. 43:269‐282.
   Humby, T., Wilkinson, L.S., Robbins, T.W., and Geyer, M.A. 1996. Prepulses inhibit startle‐induced reductions of extracellular dopamine in the nucleus accumbens of rat. J. Neurosci. 16:2149‐2156.
   Ison, J.R. and Hoffman, H.S. 1983. Reflex modifications in the domain of startle: II. The anomalous history of a robust and ubiquitous phenomenon. Psychol. Bull. 94:3‐17.
   Kehne, J.H., Padich, R.A., McCloskey, T.C., Taylor, V.L., and Schmidt, C.J. 1996. 5‐HT modulation of auditory and visual sensorimotor gating: I. Effects of 5‐HT releasers on sound and light prepulse inhibition in Wistar rats. Psychopharmacology 124:95‐106.
   Mansbach, R.S., Geyer, M.A., and Braff, D.L. 1988. Dopaminergic stimulation disrupts sensorimotor gating in the rat. Psychopharmacology 94:507‐514.
   Rigdon, G. 1990. Differential effects of apomorphine on prepulse inhibition of acoustic startle reflex in two rat strains. Psychopharmacology 102:419‐421.
   Rigdon, G.C. and Viik, K. 1991. Prepulse inhibition as a screening test for potential antipsychotics. Drug Dev. Res. 23:91‐99.
   Sipes, T.E. and Geyer, M.A. 1996. Functional behavioral homology between rat 5‐HT1B and guinea pig 5‐HT1D receptors in the modulation of prepulse inhibition of startle. Psychopharmacology 125:231‐237.
   Swerdlow, N.R., Keith, V.A., Braff, D.L., and Geyer, M.A. 1991. The effects of spiperone, raclopride, SCH 23390 and clozapine on apomorphine‐inhibition of sensorimotor gating of the startle response in the rat. J. Pharmacol. Exp. Ther. 256:530‐536.
   Swerdlow, N.R., Caine, S.B., Braff, D.L., and Geyer, M.A. 1992. Neural substrates of sensorimotor gating of the startle reflex: A review of recent findings and their implications. J. Psychopharmacol. 6:176‐190.
   Swerdlow, N.R., Braff, D.L., Caine, S.B., and Geyer, M.A. 1993. Limbic cortico‐striato‐pallido‐pontine substrates of sensorimotor gating in animal models and psychiatric disorders. In The Mesolimbic Motor Circuit and its Role in Neuropsychiatric Disorders (P. Kalivas, ed.) pp. 311‐328. CRC Press, New York.
   Swerdlow, N.R., Braff, D.L., Taaid, N., and Geyer, M.A. 1994. Assessing the validity of an animal model of sensorimotor gating deficits in schizophrenic patients. Arch. Gen. Psychiatry 51:139‐154.
Key References
   Ison and Hoffman, 1983. See
  Classical studies of the parameters controlling prestimulus modification of the startle reflex.
   Swerdlow, N.R. and Geyer, M.A. 1996. Using an animal model of deficient sensorimotor gating to study the pathophysiology and new treatments of schizophrenia. Schizophr. Bull. 20:91‐103.
  Review of the neurochemical substrates regulating prestimulus modification of startle, and their applicability to animal models of psychopathology.
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