Acute or subchronic clozapine treatment does not ameliorate prepulse inhibition (PPI) deficits in CPB-K mice with low levels of hippocampal NMDA receptor density |
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Authors: | Rainer Wolf Katrin Paelchen Kay Matzke Henrik Dobrowolny Bernhard Bogerts Herbert Schwegler |
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Institution: | (1) Department of Psychiatry, Otto-von-Guericke University, Leipziger Str. 44, 39120 Magdeburg, Germany;(2) Institute of Anatomy, Otto-von-Guericke University, Magdeburg, Germany |
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Abstract: | Introduction The hypo-glutamatergic hypothesis of schizophrenia is based on clinical similarities between schizophrenia and phencyclidine
(PCP)-induced psychosis in mentally healthy humans. Sensorimotor gating, as measured by prepulse inhibition (PPI) of the acoustic
startle response (ASR), is impaired in schizophrenic patients. In animals, noncompetitive N-methyl-d-aspartate (NMDA) antagonists such as PCP disrupt PPI in a way that resembles the defect seen in schizophrenia. In a previous
study with inbred mouse strains, low PPI levels have been demonstrated in CPB-K mice possessing low levels of hippocampal
NMDA receptor densities. The present study was performed to test whether the low magnitude of PPI in CPB-K mice can be reversed
by the atypical antipsychotic drug clozapine (CLZ).
Results Before any treatment, CPB-K mice displayed a significant (p < 0.001) lower level in PPI and a significant (p < 0.001) higher ASR when compared to BALB/cJ mice known to have high hippocampal NMDA receptor densities. Acute and subchronic
effects of a 2-week treatment with CLZ at daily doses of 5 and 10 mg/kg intraperitoneally, respectively, did not reveal any
significant alteration of PPI levels in CPB-K mice. Nevertheless, the examination of motor behavior during nonstimulus trials
provided a positive control for the drug’s effectiveness.
Conclusion In summary, (1) this study confirmed our working hypothesis: Lower levels of hippocampal glutamatergic receptor densities
correspond to lower sensorimotor gating in CPB-K mice, and (2) acute or subchronic treatment with CLZ did not elevate low
PPI levels in CPB-K mice. Thus, further experiments will concentrate on other antipsychotic drugs to prove the predictive
validity of this animal model. |
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Keywords: | CPB-K BALB/cJ NMDA Hippocampus Clozapine Sensorimotor gating Motor behavior Animal model of schizophrenia |
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