[Evaluation of antipsychotic and relative drugs using disruption of prepulse inhibition as an animal model for schizophrenia].
The prepulse inhibition (PPI) is a phenomenon in which a weak prepulse attenuates the response to a subsequent startling stimulus. The PPI, a model of sensorimotor gating, is deficient in patients with schizophrenia and some other psychiatric disorders. In rodents, PPI can be disrupted by methamphetamine or phencyclidine, which causes psychotomimetic symptoms, and the dopaminergic agonist-induced PPI is reversed by dopamine D2 receptor antagonists and a dopaminergic partial agonist aripiprazole. However, in general, the glutamate receptor antagonist-induced PPI is reversed by atypical antipsychotics such as clozapine, but not by typical antipsychotics such as haloperidol. Therefore, PPI is believed to have face, construct, and predictive validity for the PPI disruption in schizophrenia, and it is widely used as a model to study the neurobiology of this disorder and for screening antipsychotics. Recently, various inbred mouse strains and genetically modified mouse lines have been examined and the studies using PPI indicated the involvement of various neurotransmitters such as dopamine, glutamate, serotonin, GABA and neuropeptide in the biological basis of sensorimotor gating. In addtition, mood stabilizers such as valproate and lamotrigine or alpha7 nicotinic receptor agonists have reported to reverse the PPI disruption.
Suemaru
Katsuya
K
Department of Clinical Pharmacology and Pharmacy, Neuroscience, Ehime University Graduate School of Medicine, Shitsukawa, Toon 791-0295, Japan. suemaru@m.ehime-u.ac.jp
Kohnomi
Shuntaro
S
Umeda
Kenta
K
Araki
Hiroaki
H
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009538:Nicotine / Q000494:pharmacology; D010812:Physical Stimulation; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000188:drug therapy* / Q000209:etiology; D012565:Schizophrenic Psychology
D014150:Antipsychotic Agents; D009538:Nicotine