Cannabinoid receptor stimulation is anti-inflammatory and improves memory in old rats

Yannick Marchalant, Francesca Cerbai, Holly M. Brothers, Gary L. Wenk

Research output: Contribution to journalArticlepeer-review

63 Scopus citations


The number of activated microglia increase during normal aging. Stimulation of endocannabinoid receptors can reduce the number of activated microglia, particularly in the hippocampus, of young rats infused chronically with lipopolysaccharide (LPS). In the current study we demonstrate that endocannabinoid receptor stimulation by administration of WIN-55212-2 (2 mg/kg day) can reduce the number of activated microglia in hippocampus of aged rats and attenuate the spatial memory impairment in the water pool task. Our results suggest that the action of WIN-55212-2 does not depend upon a direct effect upon microglia or astrocytes but is dependent upon stimulation of neuronal cannabinoid receptors. Aging significantly reduced cannabinoid type 1 receptor binding but had no effect on cannabinoid receptor protein levels. Stimulation of cannabinoid receptors may provide clinical benefits in age-related diseases that are associated with brain inflammation, such as Alzheimer's disease.

Original languageEnglish
Pages (from-to)1894-1901
Number of pages8
JournalNeurobiology of Aging
Issue number12
StatePublished - Dec 2008
Externally publishedYes


  • Activated microglia
  • Aging
  • Cannabinoid receptors
  • Inflammation
  • Spatial memory


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