Altered regulation of glutamate release and decreased functional activity and expression of GLT1 and GLAST glutamate transporters in the hippocampus of adolescent rats perinatally exposed to Delta(9)-THC

Pharmacol Res. 2010 Apr;61(4):334-41. doi: 10.1016/j.phrs.2009.11.008. Epub 2009 Nov 24.


The long-term effects of perinatal Delta(9)-tetrahydrocannabinol (Delta(9)-THC) exposure - from gestational day (GD) 15 to postnatal day (PND) 9 - on hippocampal glutamatergic neurotransmission were studied in slices from the 40-day-old offspring of Delta(9)-THC exposed (Delta(9)-THC-rats) and vehicle-exposed (control) dams. Basal and in K+-evoked endogenous hippocampal glutamate outflow were both significantly decreased in Delta(9)-THC-rats. The effect of short Delta(9)-THC exposure (0.1microM) on K(+)-evoked glutamate release disclosed a loss of the stimulatory effect of Delta(9)-THC on hippocampal glutamate release in Delta(9)-THC-rats, but not in controls. In addition, l-[(3)H]-glutamate uptake was significantly lower in hippocampal slices from Delta(9)-THC-rats, where a significant decrease in glutamate transporter 1 (GLT1) and glutamate/aspartate transporter (GLAST) protein was also detected. Collectively, these data demonstrate that perinatal exposure to cannabinoids induces long-term impairment in hippocampal glutamatergic neurotransmission that persist into adolescence.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Dronabinol / toxicity*
  • Excitatory Amino Acid Transporter 1 / metabolism*
  • Excitatory Amino Acid Transporter 2 / metabolism*
  • Female
  • Glutamic Acid / metabolism*
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • In Vitro Techniques
  • Potassium / pharmacology
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Wistar
  • Synaptic Transmission / drug effects*


  • Excitatory Amino Acid Transporter 1
  • Excitatory Amino Acid Transporter 2
  • SLC1A3 protein, human
  • Glutamic Acid
  • Dronabinol
  • Potassium