Are DBA/2 mice associated with schizophrenia-like endophenotypes? A behavioural contrast with C57BL/6 mice

Philipp Singer, Joram Feldon, Kay Yan Benjamin Yee

Research output: Journal article publicationJournal articleAcademic researchpeer-review

42 Citations (Scopus)

Abstract

Rationale: 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. Materials and 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. Conclusion: 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.
Original languageEnglish
Pages (from-to)677-698
Number of pages22
JournalPsychopharmacology
Volume206
Issue number4
DOIs
Publication statusPublished - 1 Nov 2009
Externally publishedYes

Keywords

  • Amphetamine
  • Behavioural genetic
  • Latent inhibition
  • Mouse
  • Phencyclidine
  • Prepulse inhibition
  • Schizophrenia

ASJC Scopus subject areas

  • Pharmacology

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