Startle Habituation


Prepulse Inhibition

Prepulse inhibition (PPI) is the reduction in startle reflex amplitude that occurs when a startling stimulus is preceded 30-500 msec by a weak stimulus or prepulse. PPI is reduced in schizophrenia patients and in dopamine (DA)-activated rodents. NMDA antagonists such as phencyclidine (PCP) also disrupt PPI, and this effect is opposed by atypical antipsychotics such as clozapine, olanzapine, remoxipride, and quetiapine but not by typical antipsychotics such as haloperidol and raclopride. The ability of typical and atypical antipsychotics to restore PPI in apomorphine and PCP treated rats strongly predicts clinical antipsychotic potency.


PPI Models

• NMDA Antagonist-disrupted PPI - this model using NMDA antagonists to mimic the deficits in PPI or sensorimotor gating seen in schizophrenia may have the potential to specifically identify the current group of broad-spectrum atypical antipsychotics.

• Apomorphine-disrupted PPI - this model has excellent predictive validity for dopamine-related antipsychotics, but does not specifically identify atypical antipsychotics and is unlikely to reveal novel treatment modalities.

• Isolation Rearing Deficit in PPI- this developmental model of the deficits in gating seen in schizophrenia is sensitive to antipsychotic drugs. To date, only drugs that were expected to restore gating in isolation-reared rats have been tested and all were found to be effective, including both typical and atypical antipsychotics


PCP-induced Locomotion

The locomotor activity test is a simple means of assessing activation and arousal in animals. The animals are placed in a standard rodent cage with two infrared beams crossing the long axis. The animals are under no motivational constraints and are free to move about. Sedatives will decrease exploration and activity and stimulants usually increase exploration and activity.

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