Translational Psychiatry (Dec 2021)

Lack of direct involvement of a diazepam long-term treatment in the occurrence of irreversible cognitive impairment: a pre-clinical approach

  • Louise Carton,
  • Candice Niot,
  • Maéva Kyheng,
  • Maud Petrault,
  • Charlotte Laloux,
  • Camille Potey,
  • Marie Lenski,
  • Régis Bordet,
  • Julie Deguil

DOI
https://doi.org/10.1038/s41398-021-01718-8
Journal volume & issue
Vol. 11, no. 1
pp. 1 – 10

Abstract

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Abstract Several observational studies have found a link between the long-term use of benzodiazepines and dementia, which remains controversial. Our study was designed to assess (i) whether the long-term use of benzodiazepines, at two different doses, has an irreversible effect on cognition, (ii) and whether there is an age-dependent effect. One hundred and five C57Bl/6 male mice were randomly assigned to the 15 mg/kg/day, the 30 mg/kg/day diazepam-supplemented pellets, or the control group. Each group comprised mice aged 6 or 12 months at the beginning of the experiments and treated for 16 weeks. Two sessions of behavioral assessment were conducted: after 8 weeks of treatment and after treatment completion following a 1-week wash-out period. The mid-treatment test battery included the elevated plus maze test, the Y maze spontaneous alternation test, and the open field test. The post-treatment battery was upgraded with three additional tests: the novel object recognition task, the Barnes maze test, and the touchscreen-based paired-associated learning task. At mid-treatment, working memory was impaired in the 15 mg/kg diazepam group compared to the control group (p = 0.005). No age effect was evidenced. The post-treatment assessment of cognitive functions (working memory, visual recognition memory, spatial reference learning and memory, and visuospatial memory) did not significantly differ between groups. Despite a cognitive impact during treatment, the lack of cognitive impairment after long-term treatment discontinuation suggests that benzodiazepines alone do not cause irreversible deleterious effects on cognitive functions and supports the interest of discontinuation in chronically treated patients.