The role of L-type voltage-gated calcium channels in hippocampal CA1 neuron glutamate and GABA-A receptor-mediated synaptic plasticity following chronic benzodiazepine administration
Year: 2007
Type: article
Abstract: Withdrawal from one-week oral administration of the benzodiazepine, flurazepam (FZP) is associated with increased AMPA receptor (AMPAR) miniature excitatory postsynaptic currents (mEPSCs) but reduction of NMDA receptor (NMDAR)-evoked (e)EPSCs in hippocampal CA1 neurons.A positive correlation was observed between increased AMPAR-mediated mEPSC amplitude and anxiety-like behavior in 1-day FZP-withdrawn rats.These effects were disrupted by systemic AMPAR antagonist administration (GYKI-52466, 0.5 mg/kg, i.p.) at withdrawal onset strengthening the hypothesis that CA1 neuron AMPAR-mediated hyperexcitability is a central component of a functional anatomic circuit associated with expression of withdrawal-anxiety.Abolition of AMPAR current upregulation in 2-day FZP withdrawn rats by GYKI-52466 injection also reversed the reduction in NMDAR-mediated eEPSC amplitude in CA1 neurons from the same rats suggesting that downregulation of NMDAR function may serve a protective, negativefeedback role to prevent AMPAR-mediated neuronal over-excitation.NMDAR antagonist administration (MK-801, 0.25 mg/kg.i.p.) had no effect to modify increased glutamatergic strength or withdrawal-anxiety, while injection of an L-type VGCC antagonist, nimodipine (10 mg/kg, i.p.) averted AMPAR current enhancement and anxiety-like behavior suggesting that these manifestations may be initiated by a VGCCdependent signal transduction pathway.An evidence-based model of likely cellular mechanisms in the hippocampus contributing to benzodiazepine withdrawal-anxiety was proposed implicating regulation of multiple CA1 neuron ion channels.
Author: Kun Xiang
Institution: University of Toledo
Language: English
Subfield: Cellular and Molecular Neuroscience
Field: Neuroscience
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2218470079