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Mice deficient in the alpha subunit of Gz show changes in pre-pulse inhibition, anxiety and responses to 5-HT1A receptor stimulation, which are strongly dependent on the genetic background

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Abstract

Rationale

Gz, a member of the Gi G protein family, is involved in the coupling of dopaminergic and serotonergic receptors. In the present study, we investigated behaviour of mice deficient in the α subunit of Gz and focused on pre-pulse inhibition (PPI) and anxiety-like responses and the role of serotonin-1A (5-HT1A) receptors.

Materials and methods

We compared male and female wild-type and knock-out mice on either a C57Bl/6 or Balb/c background. We used automated startle boxes to assess startle and PPI and elevated plus maze to assess anxiety-like behaviours.

Results

Balb/c mice showed higher baseline PPI than C57Bl/6 mice, and there was no difference between the genotypes. The 5-HT1A receptor agonist, 8-hydroxy-di-propylaminotetralin (8-OH-DPAT), had no effect on PPI in C57Bl/6 mice but markedly increased PPI in Balb/c mice, with the effect being attenuated in Gαz knock-outs. On the elevated plus maze, there was little effect of the knock-out or 8-OH-DPAT in C57Bl/6 mice, whereas in Balb/c mice, Gαz knock-outs showed a phenotype of high levels of anxiety-like behaviour. 8-OH-DPAT was anxiogenic in Balb/c mice, but this effect was attenuated in Gαz knock-outs.

Conclusions

5-HT1A receptors couple to Gz. In a strictly background strain-dependent manner, Gαz knock-out mice display high levels of anxiety-like behaviour and are less sensitive to the action of 8-OH-DPAT. Balb/c mice show much more clear effects of the Gαz knock-out than C57Bl/6 mice, which are often considered the standard background strain for genetic modifications. Therefore, our results suggest caution when studying the behavioural effects of genetic modifications only in C57Bl/6 mice.

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Acknowledgements

These studies were supported by the Percy Baxter Charitable Trust, Australia. At the time of some of these experiments, the Mental Health Research Institute was a Stanley Research Centre supported by the Stanley Medical Research Institute, Bethesda, MD, USA. The authors have no conflict of interest to report.

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Authors and Affiliations

  1. Behavioural Neuroscience Laboratory, Mental Health Research Institute, 155 Oak Street, Parkville, Victoria, 3052, Australia

    Maarten van den Buuse & Sally Martin

  2. Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia

    Joan Holgate & Ian Hendry

  3. Division of Biochemistry and Molecular Biology, John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia

    Klaus Matthaei

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  1. Maarten van den Buuse
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  2. Sally Martin
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  3. Joan Holgate
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  4. Klaus Matthaei
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  5. Ian Hendry
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Correspondence to Maarten van den Buuse.

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van den Buuse, M., Martin, S., Holgate, J. et al. Mice deficient in the alpha subunit of Gz show changes in pre-pulse inhibition, anxiety and responses to 5-HT1A receptor stimulation, which are strongly dependent on the genetic background. Psychopharmacology 195, 273–283 (2007). https://doi.org/10.1007/s00213-007-0888-7

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  • DOI: https://doi.org/10.1007/s00213-007-0888-7

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