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Seroquel restores sensorimotor gating in phencyclidine-treated rats
N R Swerdlow1, V Bakshi, M A Geyer
1Department of Psychiatry and Neurosciences Program, University of California, San Diego, La Jolla 2093-0804, USA.
The Journal of Pharmacology and Experimental Therapeutics
|December 1, 1996
Summary
Seroquel effectively restored prepulse inhibition (PPI) disrupted by phencyclidine (PCP) in rats, unlike haloperidol and risperidone. This suggests Seroquel
Area of Science:
- Neuroscience
- Psychopharmacology
Background:
- Phencyclidine (PCP) disrupts prepulse inhibition (PPI) of the startle reflex, a model relevant to psychosis.
- Reduced PPI is observed in schizophrenic patients and PCP-treated animals.
Purpose of the Study:
- To evaluate the efficacy of Seroquel (ICI 204,636), a mixed D2/5-HT2 antagonist, in reversing PCP-induced PPI deficits.
- To compare Seroquel's effects with clozapine, risperidone, and haloperidol in a preclinical model of psychosis.
Main Methods:
- Rats were treated with phencyclidine (PCP) to induce PPI disruption.
- The effects of Seroquel, clozapine, risperidone, and haloperidol on PPI were assessed.
- PPI was measured by the reduction in startle reflex amplitude following a weak prepulse.
Main Results:
- PCP significantly reduced PPI in a dose-dependent manner.
- Seroquel and clozapine significantly restored PCP-induced PPI deficits.
- Haloperidol and risperidone failed to restore PPI in PCP-treated rats, though they were effective against apomorphine-induced effects.
Conclusions:
- Seroquel demonstrates preclinical antipsychotic efficacy by reversing PCP-induced PPI disruption.
- Seroquel's profile aligns with atypical antipsychotics, distinguishing it from typical antipsychotics like haloperidol and risperidone in this model.