Persistent inhibitory circuit defects and disrupted social behaviour following in utero exogenous cannabinoid exposure

Mol Psychiatry. 2017 Jan;22(1):56-67. doi: 10.1038/mp.2016.17. Epub 2016 Mar 15.


Placental transfer of Δ9-tetrahydrocannabinol (THC) during pregnancy has the potential to interfere with endogenous cannabinoid (CB) regulation of fetal nervous system development in utero. Here we examined the effect of maternal CB intake on mouse hippocampal interneurons largely focusing on cholecystokinin-expressing interneurons (CCK-INTs), a prominent CB subtype-1 receptor (CB1R) expressing neuronal population throughout development. Maternal treatment with THC or the synthetic CB1R agonist WIN55,212-2 (WIN) produced a significant loss of CCK-INTs in the offspring. Further, residual CCK-INTs in animals prenatally treated with WIN displayed decreased dendritic complexity. Consistent with these anatomical deficits, pups born to CB-treated dams exhibited compromised CCK-INT-mediated feedforward and feedback inhibition. Moreover, pups exposed to WIN in utero lacked constitutive CB1R-mediated suppression of inhibition from residual CCK-INTs and displayed altered social behavior. Our findings add to a growing list of potential cell/circuit underpinnings that may underlie cognitive impairments in offspring of mothers that abuse marijuana during pregnancy.

MeSH terms

  • Animals
  • Benzoxazines
  • Cannabinoids / adverse effects
  • Cannabinoids / metabolism
  • Cannabis / adverse effects
  • Cannabis / embryology
  • Cholecystokinin
  • Dronabinol / adverse effects*
  • Dronabinol / metabolism
  • Endocannabinoids / adverse effects
  • Endocannabinoids / metabolism
  • Female
  • Hippocampus / drug effects
  • Interneurons / drug effects
  • Mice
  • Mice, Inbred C57BL
  • Morpholines
  • Naphthalenes
  • Nervous System / drug effects*
  • Nervous System / embryology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Receptor, Cannabinoid, CB1 / metabolism
  • Receptors, Cannabinoid
  • Social Behavior


  • Benzoxazines
  • Cannabinoids
  • Endocannabinoids
  • Morpholines
  • Naphthalenes
  • Receptor, Cannabinoid, CB1
  • Receptors, Cannabinoid
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone
  • Dronabinol
  • Cholecystokinin