Prepulse inhibition is different in two inbred mouse strains (CPB-K and BALB/cJ) with different hippocampal NMDA receptor densities.
OBJECTIVE
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.


METHODS
Acoustic startle response (ASR) and prepulse inhibition (PPI) of the startle reflex were measured.


RESULTS
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.
Wolf
Rainer
R
Department of Psychiatry, Otto-von-Guericke University, D-39120 Magdeburg, Sachsen-Anhalt, Germany. Rainer.Wolf@Medizin.uni-magdeburg.de
Dobrowolny
Henrik
H
Matzke
Kay
K
Paelchen
Katrin
K
Bogerts
Bernhard
B
Schwegler
Herbert
H
D000161:Acoustic Stimulation / Q000379:methods; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D006624:Hippocampus / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D007266:Inhibition, Psychological; D051379:Mice; D008810:Mice, Inbred C57BL; D008818:Mice, Neurologic Mutants; D016194:Receptors, N-Methyl-D-Aspartate / Q000235:genetics / Q000378:metabolism*; D013216:Reflex, Startle / Q000187:drug effects / Q000502:physiology*; D015203:Reproducibility of Results; D013045:Species Specificity
D016194:Receptors, N-Methyl-D-Aspartate