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Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of Gz

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Abstract

Rationale

Gz is a member of the Gi G protein family associated with dopamine D2-like receptors; however, its functions remain relatively unknown. The aim of the present study was to investigate prepulse inhibition (PPI) of acoustic startle, locomotor hyperactivity and dopamine D2 receptor binding in mice deficient in the α subunit of Gz.

Methods

We used automated startle boxes to assess startle and PPI after treatment with saline, amphetamine, apomorphine or MK-801. We used photocell cages to quantitate locomotor activity after amphetamine treatment. Dopamine D2 receptor density was determined by autoradiography.

Results

Startle responses and baseline PPI were not different between the Gαz knockout mice and wild-type controls (average PPI 46±4 vs 49±3%, respectively). Amphetamine treatment caused a marked disruption of PPI in Gαz knockouts (average PPI 22±2%), but less so in controls (average PPI 42±3%). Similar genotype-dependent responses were seen after apomorphine treatment (average PPI 23±3% vs 40±3%), but not after MK-801 treatment (average PPI 29±5 vs 33±2%). Amphetamine-induced locomotor hyperactivity was greater in Gαz knockouts than in controls. There was no difference in the density of dopamine D2 receptors in nucleus accumbens.

Conclusions

Mice deficient in the α subunit of Gz show enhanced sensitivity to the disruption of PPI and locomotor hyperactivity caused by dopaminergic stimulation. These results suggest a possible role for Gz in neuropsychiatric illnesses with presumed dopaminergic hyperactivity, such as schizophrenia.

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Acknowledgements

The authors are grateful to Meggie Pijnappel and Sigrid Franke, Mental Health Research Institute of Victoria, Melbourne, and to Joan Holgate, Australian National University, Canberra, for assistance with the experiments. This study was supported by the National Health and Medical Research Council of Australia. M. van den Buuse was supported by the Griffith Senior Research Fellowship of the University of Melbourne. The Mental Health Research Institute is a Stanley Research Centre, supported by the Stanley Medical Research Institute.

All experiments described in this paper comply with the current laws of Australia.

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Authors and Affiliations

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

    M. van den Buuse, S. Martin & J. Brosda

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

    K. J. Leck & I. Hendry

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

    K. I. Matthaei

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  1. M. van den Buuse
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  2. S. Martin
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  3. J. Brosda
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  4. K. J. Leck
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  5. K. I. Matthaei
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  6. I. Hendry
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Correspondence to M. van den Buuse.

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van den Buuse, M., Martin, S., Brosda, J. et al. Enhanced effect of dopaminergic stimulation on prepulse inhibition in mice deficient in the alpha subunit of Gz . Psychopharmacology 183, 358–367 (2005). https://doi.org/10.1007/s00213-005-0181-6

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  • DOI: https://doi.org/10.1007/s00213-005-0181-6

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