Prenatal Cannabinoid Exposure Elicits Memory Deficits Associated with Reduced PSA-NCAM Expression, Altered Glutamatergic Signaling, and Adaptations in Hippocampal Synaptic Plasticity

Cells. 2023 Oct 26;12(21):2525. doi: 10.3390/cells12212525.


Cannabis is now one of the most commonly used illicit substances among pregnant women. This is particularly concerning since developmental exposure to cannabinoids can elicit enduring neurofunctional and cognitive alterations. This study investigates the mechanisms of learning and memory deficits resulting from prenatal cannabinoid exposure (PCE) in adolescent offspring. The synthetic cannabinoid agonist WIN55,212-2 was administered to pregnant rats, and a series of behavioral, electrophysiological, and immunochemical studies were performed to identify potential mechanisms of memory deficits in the adolescent offspring. Hippocampal-dependent memory deficits in adolescent PCE animals were associated with decreased long-term potentiation (LTP) and enhanced long-term depression (LTD) at hippocampal Schaffer collateral-CA1 synapses, as well as an imbalance between GluN2A- and GluN2B-mediated signaling. Moreover, PCE reduced gene and protein expression of neural cell adhesion molecule (NCAM) and polysialylated-NCAM (PSA-NCAM), which are critical for GluN2A and GluN2B signaling balance. Administration of exogenous PSA abrogated the LTP deficits observed in PCE animals, suggesting PSA mediated alterations in GluN2A- and GluN2B- signaling pathways may be responsible for the impaired hippocampal synaptic plasticity resulting from PCE. These findings enhance our current understanding of how PCE affects memory and how this process can be manipulated for future therapeutic purposes.

Keywords: adolescence; behavior; cannabinoid; developmental; glutamate; marijuana; memory; prenatal; synaptic plasticity.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Animals
  • Cannabinoids* / metabolism
  • Cannabinoids* / pharmacology
  • Female
  • Hippocampus / metabolism
  • Humans
  • Memory Disorders / metabolism
  • Neural Cell Adhesion Molecules* / metabolism
  • Neuronal Plasticity / physiology
  • Pregnancy
  • Rats


  • polysialyl neural cell adhesion molecule
  • Neural Cell Adhesion Molecules
  • Cannabinoids