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Different inhibitory mechanism in BALB-c and CPB/K mice using the prepulse inhibition paradigm – An animal model for schizophrenia?
Numerous evidene is available for the hyper-dopaminergic-hypothesis of schizophrenia originating in the 1950th. More recently, due to the fact that predominantly positive but not negative symptoms can be successfully treated by dopamine-blockers, other neurotransmitter candidates as serotonine, glutamate, and GABA have been suggested. According to the hypo-glutamatergic hypothesis of schizophrenia (1) we compared the two inbred mice strains BALB/c and CPB-K with considerable variations in NMDA receptor densities in different hippocampal subregions (2). Using the prepulse inhibition (PPI) paradigm CPB-K mice with lower level of NMDA receptor density displayed a significant higher acoustic startle response and a significant lower PPI level when compared to BALB/c mice. Thus, lower levels of hippocampal glutamatergic receptor densities correspond to lower sensorimotor gating as demonstrated by a higher startle response and a reduced PPI. Subsequently, pharmacological studies with clinical effective antipsychotics are performed to prove this mice strain an candidate model for schizophrenia.
1. Olney, JW et al. J.Psychiatr.Res. 33 (1999) 523–533.
2. Zilles, K et al. Hippocampus 10 (2000) 213–225.