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

作者：Castaldo Pasqualina; Magi Simona; Cataldi Mauro; Arcangeli Sara; Lariccia Vincenzo; Nasti Annamaria Assunta; Ferraro Luca; Tomasini Maria Cristina; Antonelli Tiziana; Cassano Tommaso; Cuomo Vincenzo; Amoroso Salvatore^*

来源：Pharmacological Research, 2010, 61(4): 334-341.

DOI：10.1016/j.phrs.2009.11.008

• Delta(9)-THC
• Perinatal exposure
• Glutamate release
• GLT1 and GLAST
• Hippocampus

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 (0.1 mu M) 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-[H-3]-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 persists into adolescence.

• 出版日期2010-4