Prepulse inhibition deficits in GAD65 knockout mice and the effect of antipsychotic treatment.
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.
Heldt
Scott A
SA
Center for Behavioral Neuroscience, Department of Psychiatry and Behavioral Sciences, Emory University, Atlanta, GA 30329, USA. sheldt@emory.edu
Green
Amanda
A
Ressler
Kerry J
KJ
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology; D017931:DNA Primers; D017353:Gene Deletion; D005838:Genotype; D005968:Glutamate Decarboxylase / Q000235:genetics* / Q000502:physiology*; D006185:Habituation, Psychophysiologic / Q000502:physiology; D017403:In Situ Hybridization; D007527:Isoenzymes / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D013216:Reflex, Startle / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D014150:Antipsychotic Agents; D017931:DNA Primers; D007527:Isoenzymes; D005680:gamma-Aminobutyric Acid; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2; D003024:Clozapine