title: [Disruption of prepulse inhibition of acoustic startle as an animal model for schizophrenia].
abstract: Disruption of prepulse inhibition (PPI) of acoustic startle in rats has been widely used as an animal model for the sensorimotor gating deficit state usually found in schizophrenia. PPI was reported to be regulated by forebrain circuits, including mesolimbic cortex, nucleus accumbens, ventral pallidum, thalamus, and pedunculopontine tegmentum nucleus. Phencyclidine or dopamine agonists, which causes psychotomimetic symptoms in humans, disrupts PPI in animals. The ED50 value of the drugs to reverse the phencyclidine-induced PPI disruption was significantly correlated with the affinity for the serotonin 2A receptor, but not for the dopamine D2 receptor of each drug (including atypical antipsychotics). In contrast, the ED50 value of the drugs to reverse the apomorphine-induced PPI disruption was significantly correlated with the affinity for the dopamine D2 receptor (including typical antipsychotics). Thus the drug that antagonizes the disruption of PPI caused by PCP or DA agonists would be a candidate for a therapeutic agent for the sensorimotor gating deficit state in schizophrenic patients. Neural mechanisms underlying the disruption of PPI were reviewed.
authors.affiliation: Department of Psychiatry, Saga Medical School, 5-1-1, Nabeshima, Saga, 849-8501 Japan.
authors.forename: S
authors.initials: S
authors.lastname: Yamada
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D015306:Biogenic Monoamines / Q000502:physiology; D001921:Brain / Q000502:physiology; D004195:Disease Models, Animal; D020233:Gait Disorders, Neurologic / Q000503:physiopathology / Q000523:psychology; D006801:Humans; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D017982:Receptors, Biogenic Amine / Q000502:physiology; D013216:Reflex, Startle / Q000502:physiology; D012559:Schizophrenia / Q000503:physiopathology; D012565:Schizophrenic Psychology
chemical_list: D015306:Biogenic Monoamines; D018377:Neurotransmitter Agents; D017982:Receptors, Biogenic Amine