Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice.
BACKGROUND
Due to its intrinsic deficiency in prepulse inhibition (PPI), the inbred DBA/2 mouse strain has been considered as an animal model for evaluating antipsychotic drugs. However, the PPI impairment observed in DBA/2 mice relative to the common C57BL/6 strain is confounded by a concomitant reduction in baseline startle reactivity. In this study, we examined the robustness of the PPI deficit when this confound is fully taken into account.


METHODS
Male DBA/2 and C57BL/6 mice were compared in a PPI experiment using multiple pulse stimulus intensities, allowing the possible matching of startle reactivity prior to examination of PPI. The known PPI-enhancing effect of the antipsychotic, clozapine, was then evaluated in half of the animals, whilst the other half was subjected to two additional schizophrenia-relevant behavioural tests: latent inhibition (LI) and locomotor reaction to the psychostimulants-amphetamine and phencyclidine.


RESULTS
PPI deficiency in DBA/2 relative to C57BL/6 mice was essentially independent of the strain difference in baseline startle reactivity. Yet, there was no evidence that DBA/2 mice were superior in detecting the PPI-facilitating effect of clozapine when startle difference was balanced. Compared with C57BL/6 mice, DBA/2 mice also showed impaired LI and a different temporal profile in their responses to amphetamine and phencyclidine.


CONCLUSIONS
Relative to the C57BL/6 strain, DBA/2 mice displayed multiple behavioural traits relevant to schizophrenia psycho- and physiopathology, indicative of both dopaminergic and glutamatergic/N-methyl-D: -aspartic acid receptor dysfunctions. Further examination of their underlying neurobiological differences is therefore warranted in order to enhance the power of this specific inter-strain comparison as a model of schizophrenia.
Singer
Philipp
P
Laboratory of Behavioural Neurobiology, Federal Institute of Technology Zurich, Schorenstrasse 16, Schwerzenbach, Switzerland.
Feldon
Joram
J
Yee
Benjamin K
BK
D000661:Amphetamine / Q000633:toxicity; D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology; D003024:Clozapine / Q000494:pharmacology; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D009043:Motor Activity / Q000187:drug effects; D010622:Phencyclidine / Q000633:toxicity; D010641:Phenotype; D013216:Reflex, Startle / Q000187:drug effects*; D012559:Schizophrenia / Q000503:physiopathology*; D013045:Species Specificity
D014150:Antipsychotic Agents; D000661:Amphetamine; D010622:Phencyclidine; D003024:Clozapine