H Russig1, W Spooren, S Durkin, J Feldon, B K Yee. 1. Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology, Schorenstrasse 16, 8603 Schwerzenbach, Switzerland.
Abstract
RATIONALE: Prepulse inhibition (PPI) of startle refers to the phenomenon in which a weak prepulse attenuates the startle response to a succeeding intense stimulus. PPI can be disrupted by systemic apomorphine in animals, and reduced PPI has been consistently reported in schizophrenia patients. The ability of the atypical antipsychotic clozapine to reverse apomorphine-induced PPI deficit has been demonstrated in the rat, but has not yet been tested in the mouse. The present study was designed to fill this gap. OBJECTIVE AND RESULTS: We investigated the efficacy of clozapine in reversing apomorphine-induced (2.0 or 2.5 mg/kg, s.c.) PPI deficit in C57BL6 mice. Clozapine failed to restore PPI disruption in apomorphine-treated mice in two independent laboratories across two dose ranges (1-3 mg/kg, i.p., or 3-30 mg/kg, p.o.), whereas the typical antipsychotic haloperidol (1 mg/kg, i.p.) completely normalised PPI performance. CONCLUSIONS: Unlike the rat, apomorphine-induced PPI disruption in mice might be instrumental in distinguishing between typical and atypical antipsychotic drugs. This also lends further support to the suggestion that the neuropharmacology of PPI is not identical in the two rodent species.
RATIONALE: Prepulse inhibition (PPI) of startle refers to the phenomenon in which a weak prepulse attenuates the startle response to a succeeding intense stimulus. PPI can be disrupted by systemic apomorphine in animals, and reduced PPI has been consistently reported in schizophreniapatients. The ability of the atypical antipsychotic clozapine to reverse apomorphine-induced PPI deficit has been demonstrated in the rat, but has not yet been tested in the mouse. The present study was designed to fill this gap. OBJECTIVE AND RESULTS: We investigated the efficacy of clozapine in reversing apomorphine-induced (2.0 or 2.5 mg/kg, s.c.) PPI deficit in C57BL6 mice. Clozapine failed to restore PPI disruption in apomorphine-treated mice in two independent laboratories across two dose ranges (1-3 mg/kg, i.p., or 3-30 mg/kg, p.o.), whereas the typical antipsychotic haloperidol (1 mg/kg, i.p.) completely normalised PPI performance. CONCLUSIONS: Unlike the rat, apomorphine-induced PPI disruption in mice might be instrumental in distinguishing between typical and atypical antipsychotic drugs. This also lends further support to the suggestion that the neuropharmacology of PPI is not identical in the two rodent species.
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