Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice

Abstract

Rationale

Patients suffering from Alzheimer’s disease (AD) exhibit a decline in cognitive abilities including an inability to recognise familiar faces. Hallmark pathological changes in AD include the aggregation of amyloid-β (Aβ), tau protein hyperphosphorylation as well as pronounced neurodegeneration, neuroinflammation, neurotoxicity and oxidative damage.

Objectives

The non-psychoactive phytocannabinoid cannabidiol (CBD) exerts neuroprotective, anti-oxidant and anti-inflammatory effects and promotes neurogenesis. CBD also reverses Aβ-induced spatial memory deficits in rodents.

Materials and methods

Thus we determined the therapeutic-like effects of chronic CBD treatment (20 mg/kg, daily intraperitoneal injections for 3 weeks) on the APPswe/PS1∆E9 (APPxPS1) transgenic mouse model for AD in a number of cognitive tests, including the social preference test, the novel object recognition task and the fear conditioning paradigm. We also analysed the impact of CBD on anxiety behaviours in the elevated plus maze.

Results

Vehicle-treated APPxPS1 mice demonstrated impairments in social recognition and novel object recognition compared to wild type-like mice. Chronic CBD treatment reversed these cognitive deficits in APPxPS1 mice without affecting anxiety-related behaviours.

Conclusions

This is the first study to investigate the effect of chronic CBD treatment on cognition in an AD transgenic mouse model. Our findings suggest that CBD may have therapeutic potential for specific cognitive impairments associated with AD.

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Acknowledgments

TK is supported by the Schizophrenia Research Institute utilising infrastructure funding from NSW Ministry of Health, the Motor Neuron Disease Research Institute of Australia (Mick Rodger Benalla MND Research Grant) and a career development fellowship (1045643) from the National Health and Medical Research Council (NHMRC). BG is supported by a Fellowship from the Australian Research Council (FT0991986) and is an honorary NHMRC Senior Research Fellow (630445). BG and TK are also supported by a NHMRC project grant (1003886). DC received an Australian Postgraduate Award scholarship from the University of New South Wales and a supplementary scholarship provided by Neuroscience Research Australia. We thank Jerry Tanda for the critical comments on the manuscript, the staff of the Australian BioResources and Adam Bryan at Neuroscience Research Australia for taking care of our test mice.

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Correspondence to Tim Karl.

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Cheng, D., Low, J.K., Logge, W. et al. Chronic cannabidiol treatment improves social and object recognition in double transgenic APPswe/PS1∆E9 mice. Psychopharmacology 231, 3009–3017 (2014). https://doi.org/10.1007/s00213-014-3478-5

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Keywords

  • Alzheimer’s disease
  • Novel therapeutic
  • Cannabidiol
  • Transgenic APPswe/PS1∆E9 mice
  • Cognition
  • Behaviour
  • Social recognition memory
  • Object recognition memory