Downregulation of endocannabinoid signaling in the hippocampus following chronic unpredictable stress

Matthew N. Hill, Sachin Patel, Erica J. Carrier, David J. Rademacher, Brandi K. Ormerod, Cecilia J. Hillard, Boris B. Gorzalka*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

288 Scopus citations

Abstract

Deficits in cognitive functioning and flexibility are seen following both chronic stress and modulation of endogenous cannabinoid (eCB) signaling. Here, we investigated whether alterations in eCB signaling might contribute to the cognitive impairments induced by chronic stress. Chronic stress impaired reversal learning and induced perseveratory behavior in the Morris water maze without significant effect on task acquisition. These cognitive impairments were reversed by exogenous cannabinoid administration, suggesting deficient eCB signaling underlies these phenomena. In line with this hypothesis, chronic stress downregulated CB1 receptor expression and significantly reduced the content of the endocannabinoid 2-arachidonylglycerol within the hippocampus. CB1 receptor density and 2-arachidonylglycerol content were unaffected in the limbic forebrain. These data suggest that stress-induced downregulation of hippocampal eCB signaling contributes to problems in behavioral flexibility and could play a role in the development of perseveratory and ruminatory behaviors in stress-related neuropsychiatric disorders.

Original languageEnglish (US)
Pages (from-to)508-515
Number of pages8
JournalNeuropsychopharmacology
Volume30
Issue number3
DOIs
StatePublished - Mar 2005
Externally publishedYes

Keywords

  • 2-arachidonylglycerol
  • CB
  • Chronic stress
  • Endocannabinoid
  • Hippocampus
  • Perseveration

ASJC Scopus subject areas

  • Pharmacology
  • Psychiatry and Mental health

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