Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia

doi:10.1016/0006-3223(93)90180-L

Biological Psychiatry

Volume 34, Issue 6, 15 September 1993, Pages 361-372

https://doi.org/10.1016/0006-3223(93)90180-L Get rights and content

Abstract

Schizophrenic patients exhibit deficits in the prepulse inhibition of startle, an operational measure of the sensorimotor gating deficits that are theorized to contribute to cognitive disorganization. In rats, the activation of mesolimbic dopamine (DA) disrupts prepulse inhibition, providing a useful model of the similar deficits in sensorimotor gating in schizophrenic patients. Rats reared in isolation exhibit neurochemical and behavioral abnormalities suggestive of hyperactivity in mesolimbic DA systems. In the present studies, rats reared in social groups or in isolation were tested in startle response paradigms using 120 or 105 dB acoustic pulses, some of which were preceded (100 msec) by prepulses that were 2, 4, 8, or 16 dB above the 65 dB background. Isolation-reared animals were hyperreactive only in response to the initial few startle stimuli. The amount of prepulse inhibition was decreased significantly in isolation-reared animals, particularly when midrange 8 dB prepulses were used. A subsequent study replicated the effect of isolation rearing on prepulse inhibition and suggested that the deficit in sensorimotor gating exhibited by isolation-reared animals may be normalized by the administration of the DA antagonist raclopride (0.05 mg/kg). Hence, isolation rearing provides a nonpharmacological way to induce in rats a deficit in sensorimotor gating that is exhibited by schizophrenic patients.

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^☆: This work was supported in part by a grant from the National Institute of Mental Health (MH42228, D.L. Braff, PI) and in part by a Pilot Project grant from the John D. and Catherine T. MacArthur Foundation Mental Health Network I: The Psychobiology of Depression and Other Affective Disorders.

¹: M.A. Geyer was supported by a Research Scientist Development Award from the National Institute of Mental Health (MH00188).

²: We thank D. L. Braff and anonymous reviewers for constructive comments on the manuscript.

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Isolation rearing of rats produces a deficit in prepulse inhibition of acoustic startle similar to that in schizophrenia☆

Abstract

Pharmacol Biochem Behav

Physiol Behav

Pharmacol Biochem Behav

Brain Res Bull

Eur J Pharmacol

Behav Brain Research

Pharmacol Biochem Behav

Eur J Pharmacol

Physiol Behav

Brain Res

Physiol Behav

Neurosci Lett

Pharmacol Biochem Behav

Response to stress of mesocortical-frontal dopaminergic neurons in rats after long-term isolation

Nature

Sensorimotor gating and schizophrenia: Human and animal model studies

Arch Gen Psychiatry

Gating and habituation of the startle reflex in schizophrenic patients

Arch Gen Psychiatry

Prestimulus effects on human startle reflex in normals and schizophrenics

Psychophysiology

Impaired startle prepulse inhibition and habituation in schizotypal patients

Am J Psychiatry

Carbachol infusion into the dentate gyrus disrupts sensorimotor gating of startle in the rat

Psychopharmacology

Apomorphine disrupts the inhibition of acoustic startle induced by weak prepulses in rats

Psychopharmacology

BMDP Biomedical Computer Programs

Early isolation produced enduring hyperactivity in the rat but no effects on spontaneous alternation

Q J Exp Psychol