Cannabidiol attenuates cognitive deficits and neuroinflammation induced by early alcohol exposure in a mice model

Biomed Pharmacother. 2021 Sep:141:111813. doi: 10.1016/j.biopha.2021.111813. Epub 2021 Jun 11.

Abstract

Foetal alcohol spectrum disorder (FASD) is the umbrella term used to describe the physical and mental disabilities induced by alcohol exposure during development. Early alcohol exposure induces cognitive impairments resulting from damage to the central nervous system (CNS). The neuroinflammatory response accompanied by neurodegenerative mechanisms contribute to those detrimental alterations. Cannabidiol (CBD) has recently emerged as an anti-inflammatory drug that might be useful to treat several neuropsychiatric disorders. In our study, we assessed the effects of CBD on long-lasting cognitive deficits induced by early alcohol exposure. Furthermore, we analysed long-term pro-inflammatory and apoptotic markers within the prefrontal cortex and hippocampus. To model alcohol binge drinking during gestational and lactation periods, we used pregnant C57BL/6 female mice with time-limited access to 20% v/v alcohol solution. Following the prenatal and lactation alcohol exposure (PLAE), we treated the male and female offspring with CBD from post-natal day (PD) 25 until PD34, and we evaluated their cognitive performance at PD60. Our results showed that CBD treatment during peri-adolescence period ameliorates cognitive deficits observed in our FASD-like mouse model, without sex differences. Moreover, CBD restores the PLAE-induced increased levels of TNFα and IL-6 in the hippocampus. Thus, our study provides new insights for CBD as a therapeutic agent to counteract cognitive impairments and neuroinflammation caused by early alcohol exposure.

Keywords: Cannabidiol; Cannabidiol (PubChem CID: 644019); Cognitive deficits; Ethanol (PubChem CID: 702); Foetal alcohol spectrum disorder; Neuroinflammation; Prenatal alcohol exposure.

MeSH terms

  • Animals
  • Binge Drinking / complications
  • Cannabidiol / therapeutic use*
  • Cognitive Dysfunction / chemically induced
  • Cognitive Dysfunction / drug therapy*
  • Cognitive Dysfunction / psychology
  • Disease Models, Animal
  • Encephalitis / chemically induced
  • Encephalitis / drug therapy*
  • Female
  • Fetal Alcohol Spectrum Disorders / drug therapy*
  • Hippocampus / pathology
  • Male
  • Memory / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Prefrontal Cortex / pathology
  • Pregnancy
  • Psychomotor Performance / drug effects
  • Rats
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Cannabidiol