Skip Navigation

Schizophrenia Bulletin 1998 24(2):285-301;
© 1998 by Oxford University Press and the Maryland Psychiatric Research Center (MPRC)
This Article
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Swerdlow, N. R.
Right arrow Articles by Geyer, M. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Swerdlow, N. R.
Right arrow Articles by Geyer, M. A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© Oxford University Press

Using an Animal Model of Deficient Sensorimotor Gating to Study the Pathophysiology and New Treatments of Schizophrenia

Neal R. Swerdlow, M.D., Ph.D. and Mark A. Geyer, Ph.D.
Assistant Professor, Department of Psychiatry, University of California at San Diego La Jolla, CA
Professor in Residence, Department of Psychiatry, University of California at San Diego La Jolla, CA

Reprint requests should be Sent to Dr. N.R. Swerdlow, Dept. of Psychiatry, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0804

Certain animal models can greatly enhance our understanding of the neurobiology of schizophrenia and can be used to predict the antipsychotic activity of compounds. Prepulse inhibition (PPI), the reduction in startle produced by a prepulse stimulus, is diminished in schizophrenia patients. Theoretically, deficient PPI in schizophrenia patients is a measure of the loss of sensorimotor gating that may lead to sensory flooding and cognitive fragmentation. In rats, PPI is disrupted by systemic administration of dopamine agonists, serotonin agonists, or glutamate antagonists and by a variety of surgical or pharmacological manipulations of neural circuitry linking the limbic cortex, striatum, pallidum, and pontine reticular formation. This article describes several different ways the loss of PPI in rats can be used as a model for studying the pathophysiology and neurobiology of impaired sensorimotor gating in schizophrenia patients and for predicting antipsychotic activity in novel compounds. First, new experimental strategies may be used to distinguish behavioral profiles of "typical" versus "atypical" antipsychotics. Second, this paradigm can be used to study the effects of early developmental insults—including neonatal lesions and isolated rearing—on the adult emergence of deficient sensorimotor gating. Third, using different animal strains and species, as well as gene "knockout" strategies, greatly increases our ability to understand specific genetic or receptor contributions to the regulation of deficient PPI. Each of these uses of the PPI paradigm is enhanced by studies of the basic brain substrates that regulate PPI in rats and by the increasingly sophisticated assessments of PPI and related measures in schizophrenia spectrum patients.

Keywords: Animal models / antipsychotics / prepulse inhibition / sensorimotor gating


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Schizophr BullHome page
B. B. Quednow, M. Wagner, R. Mossner, W. Maier, and K.-U. Kuhn
Sensorimotor Gating of Schizophrenia Patients Depends on Catechol O-Methyltransferase Val158Met Polymorphism
Schizophr Bull, July 17, 2008; (2008) sbn088v1.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurophysiol.Home page
H. Neumeister, T. M. Szabo, and T. Preuss
Behavioral and Physiological Characterization of Sensorimotor Gating in the Goldfish Startle Response
J Neurophysiol, March 1, 2008; 99(3): 1493 - 1502.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
M. Mizuno, H. Sotoyama, E. Narita, H. Kawamura, H. Namba, Y. Zheng, T. Eda, and H. Nawa
A Cyclooxygenase-2 Inhibitor Ameliorates Behavioral Impairments Induced by Striatal Administration of Epidermal Growth Factor
J. Neurosci., September 19, 2007; 27(38): 10116 - 10127.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. PsychiatryHome page
F. Ferrarelli, R. Huber, M. J. Peterson, M. Massimini, M. Murphy, B. A. Riedner, A. Watson, P. Bria, and G. Tononi
Reduced Sleep Spindle Activity in Schizophrenia Patients
Am J Psychiatry, March 1, 2007; 164(3): 483 - 492.
[Abstract] [Full Text] [PDF]

Home page
 J. Neurosci.Home page
K. Tanaka, N. Shintani, H. Hashimoto, N. Kawagishi, Y. Ago, T. Matsuda, R. Hashimoto, H. Kunugi, A. Yamamoto, C. Kawaguchi, et al.
Psychostimulant-induced attenuation of hyperactivity and prepulse inhibition deficits in Adcyap1-deficient mice.
J. Neurosci., May 10, 2006; 26(19): 5091 - 5097.
[Abstract] [Full Text] [PDF]

Home page
 BrainHome page
A. R. Aron, F. Schlaghecken, P. C. Fletcher, E. T. Bullmore, M. Eimer, R. Barker, B. J. Sahakian, and T. W. Robbins
Inhibition of subliminally primed responses is mediated by the caudate and thalamus: evidence from functional MRI and Huntington's disease
Brain, March 1, 2003; 126(3): 713 - 723.
[Abstract] [Full Text] [PDF]

Home page
 Behav Cogn Neurosci RevHome page
D. S. Woodruff-Pak and T. J. Gould
Neuronal nicotinic acetylcholine receptors: involvement in Alzheimer's disease and schizophrenia.
Behav Cogn Neurosci Rev, March 1, 2002; 1(1): 5 - 20.
[Abstract] [PDF]


Disclaimer:
Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.