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 Δ9-THC

The long-term effects of perinatal Δ9-tetrahydrocannabinol (Δ9-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 Δ9-THC exposed (Δ9-THC-rats) and vehicle-exposed (control) dams. Basal and in K+-evoked endogenous hippocampal glutamate outflow were both significantly decreased in Δ9-THC-rats. The effect of short Δ9-THC exposure (0.1 μM) on K+-evoked glutamate release disclosed a loss of the stimulatory effect of Δ9-THC on hippocampal glutamate release in Δ9-THC-rats, but not in controls. In addition, l-[3H]-glutamate uptake was significantly lower in hippocampal slices from Δ9-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.