Prepulse inhibition is different in two inbred mouse strains (CPB-K and BALB/cJ) with different hippocampal NMDA receptor densities.
Rainer Wolf, Henrik Dobrowolny, Kay Matzke, Katrin Paelchen, Bernhard Bogerts, Herbert Schwegler
Behavioural Brain Research January 6, 2006 DOI: 10.1016/j.bbr.2005.07.027 (opens in new tab) via PubMed
Summary
AI-generated from the abstractMice with lower NMDA receptor density in the hippocampus (CPB-K strain) show weaker sensorimotor gating—measured by prepulse inhibition (PPI)—compared to mice with higher receptor density (BALB/cJ strain). CPB-K mice also had a significantly higher acoustic startle response. PPI was reliably measured across repeated sessions over 13 weeks. The authors propose that the CPB-K mouse strain may serve as an animal model for schizophrenia, consistent with the hypo-glutamatergic hypothesis of the disorder, but further behavioral experiments are needed to establish this.
Study at a glance
| Characteristics | Animal study Peer reviewed |
|---|---|
| Population | CPB-K and BALB/cJ inbred mouse strains |
| Duration | Repeated sessions over 13 weeks |
| Key finding | CPB-K mice, which have lower hippocampal NMDA receptor density, show significantly lower prepulse inhibition and higher acoustic startle response compared to BALB/cJ mice. |
Abstract
The hypo-glutamatergic hypothesis of schizophrenia is not only based on the phencyclidine-(PCP)-induced psychosis in mentally healthy humans but also on studies with schizophrenic patients showing deficits in post mortem hippocampal N-methyl-d-aspartate (NMDA) receptor gene expression and deficits in prepulse inhibition. The inbred mouse strains CPB-K and BALB/cJ display considerable differences in hippocampal NMDA receptor densities. Therefore, our working hypothesis was based on the assumption that the CPB-K mouse strain, which has a lower NMDA receptor density in hippocampal CA1, might be a possible animal model for schizophrenia. For this purpose, the inbred mouse strains CPB-K and BALB/cJ were compared by using a sensorimotor gating paradigm. Acoustic startle response (ASR) and prepulse inhibition (PPI) of the startle reflex were measured. CPB-K mice displayed a significantly higher ASR and a significantly lower magnitude of PPI as compared to BALB/cJ mice. The test-retest reliability was approved for PPI in both mouse strains, which was performed in repeated sessions over 13 weeks. In summary, our working hypothesis was confirmed that lower levels of hippocampal NMDA receptor densities correspond to lower sensorimotor gating in CPB-K mice. Based on this finding, further experiments using different behavioral paradigms have to be carried out to establish the CPB-K mouse strain as an animal model of schizophrenia.