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A follow-up study: acute behavioural effects of Δ9-THC in female heterozygous Neuregulin 1 transmembrane domain mutant mice

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Abstract

Rationale

Heavy cannabis use is linked with an increased risk for schizophrenia. We showed previously that male heterozygous neuregulin 1 transmembrane domain (Nrg1 HET) mice are more sensitive to some effects of the psychotropic cannabis constituent Δ9-tetrahydrocannabinol (THC). We report data from a follow-up study in female Nrg1 HET mice, investigating THC effects on behaviours with some relevance to schizophrenia.

Methods

Mice were injected with THC (0, 5 or 10 mg/kg i.p.) 30 min before a test battery: open field, elevated plus maze, novel object recognition (set 1) or light–dark, social interaction (SI) and prepulse inhibition (PPI 1: variable interstimulus interval (ISI); set 2). Another set (set 3) was injected with the same doses of THC before a fixed interstimulus interval PPI test (PPI 2).

Results

Female Nrg1 HETs displayed the hallmark increased locomotor activity at 5 months and anxiolytic-like behaviour in the open field at 3 and 5 months. THC decreased locomotor activity in both genotypes. THC selectively reduced some SI behaviours in WT mice. Baseline PPI was enhanced in mutants under a variable ISI, while THC had no effect on PPI using either protocol.

Conclusions

This study reports novel findings on the baseline PPI profile and resistance to THC-induced social withdrawal in female Nrg1 HET mice. This is the first description of THC effects in females of this mouse model and suggests that the transmembrane domain Nrg1 mutation does not appear to have a severe impact on the behavioural sensitivity to THC in female mice.

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Acknowledgements

This work was supported by the Schizophrenia Research Institute, utilising infrastructure funding from NSW Health, and by the Sylvia and Charles Viertel Charitable Foundation. TK was supported by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award, a Biomedical Research Award from the Clive and Vera Ramaciotti Foundation, a National Health and Medical Research Council (NHMRC) CDA (568752) and a NHMRC project grant (493301), which was also awarded to JCA and other investigators. We thank Ms. Britta Wenske for technical assistance, the biological testing facility staff (E. Cairns and M. Pickering) for their support and Jerry Tanda for her critical comments on this manuscript.

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Authors and Affiliations

  1. Schizophrenia Research Institute, 405 Liverpool St., Darlinghurst, NSW, 2010, Australia

    Leonora E. Long, Rose Chesworth, Jonathon C. Arnold & Tim Karl

  2. Garvan Institute of Medical Research, Darlinghurst, NSW, 2010, Australia

    Leonora E. Long, Rose Chesworth & Tim Karl

  3. Department of Pharmacology, University of Sydney, Sydney, NSW, 2006, Australia

    Jonathon C. Arnold

  4. Neuroscience Research Australia (NeuRA), Randwick, NSW, 2031, Australia

    Leonora E. Long, Rose Chesworth & Tim Karl

  5. School of Medical Sciences, University of New South Wales, Kensington, NSW, 2052, Australia

    Leonora E. Long

  6. St Vincent’s Clinical School, University of New South Wales, Kensington, NSW, 2052, Australia

    Tim Karl

  7. Brain and Mind Research Institute, University of Sydney, Sydney, NSW, 2006, Australia

    Jonathon C. Arnold

Authors
  1. Leonora E. Long
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  2. Rose Chesworth
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  3. Jonathon C. Arnold
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  4. Tim Karl
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Corresponding authors

Correspondence to Leonora E. Long or Tim Karl.

Additional information

Research supported by the Schizophrenia Research Institute, utilising infrastructure funding from NSW Health, and by the Sylvia and Charles Viertel Charitable Foundation. TK was supported by a National Alliance for Research on Schizophrenia and Depression Young Investigator Award, a Biomedical Research Award from the Clive and Vera Ramaciotti Foundation, a National Health and Medical Research Council (NHMRC) CDA (568752) and a NHMRC project grant (493301), which was also awarded to JCA and other investigators.

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Long, L.E., Chesworth, R., Arnold, J.C. et al. A follow-up study: acute behavioural effects of Δ9-THC in female heterozygous Neuregulin 1 transmembrane domain mutant mice. Psychopharmacology 211, 277–289 (2010). https://doi.org/10.1007/s00213-010-1896-6

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  • DOI: https://doi.org/10.1007/s00213-010-1896-6

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