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Reduced expression of glutamate receptors and phosphorylation of CREB are responsible for in vivo Δ9‐THC exposure‐impaired hippocampal synaptic plasticity
Author(s) -
Fan Ni,
Yang Hongwei,
Zhang Jian,
Chen Chu
Publication year - 2010
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2009.06489.x
Subject(s) - long term potentiation , creb , synaptic plasticity , ampa receptor , glutamate receptor , long term depression , neuroscience , nmda receptor , neurotransmission , hippocampal formation , glutamatergic , biology , metaplasticity , chemistry , receptor , biochemistry , transcription factor , gene
J. Neurochem. (2010) 112 , 691–702. Abstract Chronic use of marijuana impairs synaptic plasticity and cognitive function. However, the molecular mechanisms by which marijuana alters long‐term synaptic plasticity are largely unknown. Here, we show that repeated in vivo exposures to Δ9‐THC for 7 consecutive days significantly impaired hippocampal long‐term potentiation (LTP) of excitatory glutamatergic synaptic transmission. The Δ9‐THC exposure‐induced decrease in LTP was prevented by pharmacological inhibition or deletion of the cannabinoid 1 receptor (CB1R). To determine the molecular mechanisms underlying Δ9‐THC‐altered LTP, we targeted expression and function of the glutamate receptors (GluR) and phosphorylation status of cAMP‐response element‐binding protein (CREB). Chronic in vivo exposure to Δ9‐THC produced CB1R‐dependent decreases in expression of hippocampal GluR1, NR2A, and NR2B, the ratio of α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate (AMPA)/NMDA receptor‐gated currents, and phosphorylation of CREB. Our results suggest that reduced expression and function of the GluR subunits and phosphorylation of CREB may underlie the impaired long‐term synaptic plasticity induced by repeated in vivo exposure to Δ9‐THC.