Short- and long-term consequences of prenatal exposure to the cannabinoid agonist WIN55,212-2 on rat glutamate transmission and cognitive functions

J Neural Transm (Vienna). 2009 Aug;116(8):1017-27. doi: 10.1007/s00702-009-0230-0. Epub 2009 May 12.


The aim of the present review is to summarize integrated neurochemical, morphological and neurobehavioral evidence, in particular from our laboratory, which emphasize the short- and long-term consequences of prenatal exposure to the cannabinoid receptor agonist WIN55,212-2 on rat glutamate transmission and cognitive functions. The results obtained provide evidence that maternal exposure to WIN55,212-2 induces an impairment of cognitive capacities in the offspring. This impairment is associated with alterations of cortical and hippocampal glutamate outflow, cortical neuron morphology and hippocampal long-term potentiation. These findings are in line with clinical data showing that the consumption of marijuana by women during pregnancy has negative consequences on the cognitive functions of their children. Thus, although it is difficult and sometimes misleading to extrapolate findings obtained from animal models to humans, the possibility that an alteration of glutamate transmission might underlie, at least in part, some of the cognitive deficits affecting the offspring of marijuana users, is supported.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging
  • Animals
  • Benzoxazines / pharmacology*
  • Cannabinoid Receptor Agonists*
  • Cannabinoids / pharmacology
  • Cerebral Cortex / cytology
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / physiology
  • Cognition / drug effects*
  • Cognition / physiology
  • Emotions / drug effects
  • Emotions / physiology
  • Female
  • Glutamic Acid / metabolism*
  • Hippocampus / cytology
  • Hippocampus / drug effects
  • Hippocampus / physiology
  • Humans
  • Learning / drug effects
  • Learning / physiology
  • Morpholines / pharmacology*
  • Naphthalenes / pharmacology*
  • Neurons / cytology
  • Neurons / drug effects
  • Neurons / physiology
  • Pregnancy
  • Prenatal Exposure Delayed Effects*
  • Rats
  • Synaptic Transmission / drug effects*
  • Synaptic Transmission / physiology
  • Time Factors


  • Benzoxazines
  • Cannabinoid Receptor Agonists
  • Cannabinoids
  • Morpholines
  • Naphthalenes
  • Glutamic Acid
  • (3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone