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Long-term cognitive impairments induced by chronic cannabinoid exposure during adolescence in rats: a strain comparison

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Abstract

Rationale

During cerebral development, adolescence is a critical phase in which the endocannabinoid system plays an important role in regulating various neurotransmitters. Moreover, evidence from both human and animal studies suggests that chronic cannabinoid exposure during this vulnerable period can induce persistent brain and behavioural alterations.

Objectives

The aim of this study was to compare the long-term cognitive consequences of chronic adolescence cannabinoid exposure between Lister Hooded rats and Wistar rats.

Methods

Rats of both strains were injected daily throughout their adolescent or adult periods with vehicle or with incremental doses of the synthetic cannabinoid CB1 receptor agonist CP55,940 (CP). Short-term and spatial working memories were assessed using the object recognition and object location, tasks respectively. For both tasks, the effect of a 30- or 120-min delay between the learning and the testing phase was investigated.

Results

In the object recognition task, adolescent CP exposure impaired short-term memory after both delays in both strains. In contrast, in the object location task, adolescent CP exposure impaired spatial working memory in the Wistar rats after a 30-min delay, whereas the Lister Hooded rats exhibited a similar effect only after a 120-min delay. In these tests, no long-term deleterious effects were found following adult CP exposure in either strain.

Conclusions

Our results confirm that adolescence is a critical period for the deleterious effects of cannabinoids on cognition and that these deleterious effects on spatial working memory are more strain-dependent than the effects observed on short-term memory.

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Acknowledgments

This study was supported by funds from the French National Research Agency (ANR-06-NEURO-044-01). We thank Julie Cognet for her technical assistance.

Conflict of interest

All authors declare that they have no conflicts of interest

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Authors and Affiliations

  1. Laboratoire de “Physiopathologie des maladies Psychiatriques”, Centre de Psychiatrie et Neurosciences U894, INSERM, Paris, France

    Justine Renard, Marie-Odile Krebs, Thérèse M. Jay & Gwenaëlle Le Pen

  2. Faculté de Médecine Paris Descartes, Université Paris Descartes, Paris, France

    Justine Renard, Marie-Odile Krebs, Thérèse M. Jay & Gwenaëlle Le Pen

  3. Centre de Psychiatrie et de Neurosciences, INSERM U894, 2ter rue d’Alésia, 75014, Paris, France

    Gwenaëlle Le Pen

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  1. Justine Renard
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  2. Marie-Odile Krebs
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  3. Thérèse M. Jay
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  4. Gwenaëlle Le Pen
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Correspondence to Gwenaëlle Le Pen.

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Thérèse M. Jay and Gwenaëlle Le Pen contributed equally to this work.

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Renard, J., Krebs, MO., Jay, T.M. et al. Long-term cognitive impairments induced by chronic cannabinoid exposure during adolescence in rats: a strain comparison. Psychopharmacology 225, 781–790 (2013). https://doi.org/10.1007/s00213-012-2865-z

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  • DOI: https://doi.org/10.1007/s00213-012-2865-z

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