Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment

Scott Heldt, Amanda Green, Kerry J. Ressler

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Recent postmortem studies in humans suggest that defects in GABAergic neurotransmission might contribute to the neuropathology associated with schizophrenia. Disturbances in GABAergic systems may also contribute to the sensorimotor gating deficits classically observed in schizophrenic patients, including deficits in prepulse inhibition (PPI). To explore the relationship, the current study examined the integrity of PPI and startle habituation in knockout (KO) mice that lack the GABA synthesizing enzyme glutamic acid decarboxylase 65 (GAD 65). GAD65 KO mice displayed normal baseline and habituated startle responses, which did not differ from GAD65 wild-type (WT) or heterozygous (HET) mice. However, GAD65 KO mice showed robust deficits in PPI which were reversed by the atypical antipsychotic agent clozapine. These results lend support to the view that abnormalities in GABAergic systems might contribute to the basic pathophysiological mechanisms in schizophrenia.

Original languageEnglish (US)
Pages (from-to)1610-1619
Number of pages10
JournalNeuropsychopharmacology
Volume29
Issue number9
DOIs
StatePublished - Sep 1 2004

Fingerprint

Knockout Mice
Antipsychotic Agents
Schizophrenia
Startle Reflex
Sensory Gating
Glutamate Decarboxylase
Clozapine
Synaptic Transmission
gamma-Aminobutyric Acid
Therapeutics
Enzymes
Prepulse Inhibition

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Psychiatry and Mental health

Cite this

Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment. / Heldt, Scott; Green, Amanda; Ressler, Kerry J.

In: Neuropsychopharmacology, Vol. 29, No. 9, 01.09.2004, p. 1610-1619.

Research output: Contribution to journalArticle

Heldt, Scott ; Green, Amanda ; Ressler, Kerry J. / Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment. In: Neuropsychopharmacology. 2004 ; Vol. 29, No. 9. pp. 1610-1619.
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