Disruption of prepulse inhibition following N-methyl-D-aspartate infusion into the ventral hippocampus is antagonized by clozapine but not by haloperidol: a possible model for the screening of atypical antipsychotics.
The present study tested the effects of the typical neuroleptic haloperidol and an atypical neuroleptic clozapine on ventral hippocampus stimulation-induced disruption of prepulse inhibition (PPI). Bilateral infusions of 0.7 microg NMDA into the ventral hippocampus disrupted PPI. The impairment of PPI following the infusion was completely normalized 24 h after the infusion. This disruption of PPI was antagonized by clozapine (5.0 mg/kg), but not by haloperidol (0.2 mg/kg). Since disruption of PPI is considered to constitute an animal model of schizophrenia that is related to the deficit of sensorimotor gating observed in schizophrenic patients, these results suggest that PPI disruption induced by intra-ventral hippocampal infusions of NMDA may serve as an animal model for the selective detection of atypical antipsychotics.
Zhang
W
W
Behavioural Biology Laboratory, Swiss Federal Institute of Technology Zurich.
Pouzet
B
B
Jongen-Rêlo
A L
AL
Weiner
I
I
Feldon
J
J
D000161:Acoustic Stimulation; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D003024:Clozapine / Q000494:pharmacology*; D004195:Disease Models, Animal; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects*; D007263:Infusions, Parenteral; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013216:Reflex, Startle / Q000187:drug effects*
D014150:Antipsychotic Agents; D018691:Excitatory Amino Acid Antagonists; D016202:N-Methylaspartate; D003024:Clozapine; D006220:Haloperidol