Benzodiazepine-induced hippocampal CA1 neuron alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors.
Behav Pharmacol. 2007 Sep; 18(5-6):447-60.BP

Abstract

Withdrawal from 1-week oral administration of the benzodiazepine, flurazepam (FZP) is associated with increased alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor (AMPAR) miniature excitatory postsynaptic currents (mEPSCs) but reduction of N-methyl-D-aspartic acid (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correlation was observed between increased AMPAR-mediated mEPSC amplitude and anxiety-like behavior in 1-day FZP-withdrawn rats.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, intraperitoneal) at withdrawal onset, strengthening the hypothesis that CA1 neuron AMPAR-mediated hyperexcitability is a central component of a functional anatomic circuit associated with the 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 Abolition of AMPAR current upregulation in 2-day FZP withdrawn rats by GYKI-52466 injection also reversed the reduction in NMDAR-mediated eEPSC amplitude in CA1 neurons from the same rats, suggesting that downregulation of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, negative-feedback role to prevent AMPAR-mediated neuronal overexcitation. NMDAR antagonist administration (MK-801, 0.25 mg/kg intraperitoneally) had no effect on modifying increased glutamatergic strength or on withdrawal anxiety, whereas injection of an L-type voltage-gated calcium channel antagonist, nimodipine (10 mg/kg, intraperitoneally) averted AMPAR current enhancement and anxiety-like behavior, suggesting that these manifestations may be initiated by a voltage-gated calcium channel-dependent 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.

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Authors+Show Affiliations

Xiang K

Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, Toledo, Ohio 43614, USA.

Tietz EI

No affiliation info available

MeSH

AnimalsAnxietyBenzodiazepinesCalcium Channels, L-TypeDisease Models, AnimalDizocilpine MaleateDown-RegulationExcitatory Postsynaptic PotentialsFlurazepamHippocampusMaleNeuronal PlasticityRatsRats, Sprague-DawleyReceptors, AMPAReceptors, N-Methyl-D-AspartateSeverity of Illness IndexSignal TransductionSubstance Withdrawal Syndrome

Pub Type(s)

Journal Article

Research Support, N.I.H., Extramural

Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17762513

Citation

Xiang, Kun, and Elizabeth I. Tietz. "Benzodiazepine-induced Hippocampal CA1 Neuron Alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic Acid (AMPA) Receptor Plasticity Linked to Severity of Withdrawal Anxiety: Differential Role of Voltage-gated Calcium Channels and N-methyl-D-aspartic Acid Receptors." Behavioural Pharmacology, vol. 18, no. 5-6, 2007, pp. 447-60.

Xiang K, Tietz EI. Benzodiazepine-induced hippocampal CA1 neuron alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors. Behav Pharmacol. 2007;18(5-6):447-60.

Xiang, K., & Tietz, E. I. (2007). Benzodiazepine-induced hippocampal CA1 neuron alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors. Behavioural Pharmacology, 18(5-6), 447-60.

Xiang K, Tietz EI. Benzodiazepine-induced Hippocampal CA1 Neuron Alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic Acid (AMPA) Receptor Plasticity Linked to Severity of Withdrawal Anxiety: Differential Role of Voltage-gated Calcium Channels and N-methyl-D-aspartic Acid Receptors. Behav Pharmacol. 2007;18(5-6):447-60. PubMed PMID: 17762513.

* Article titles in AMA citation format should be in sentence-case

TY - JOUR T1 - Benzodiazepine-induced hippocampal CA1 neuron alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor plasticity linked to severity of withdrawal anxiety: differential role of voltage-gated calcium channels and N-methyl-D-aspartic acid receptors. AU - Xiang,Kun, AU - Tietz,Elizabeth I, PY - 2007/9/1/pubmed PY - 2007/10/24/medline PY - 2007/9/1/entrez SP - 447 EP - 60 JF - Behavioural pharmacology JO - Behav Pharmacol VL - 18 IS - 5-6 N2 - Withdrawal from 1-week oral administration of the benzodiazepine, flurazepam (FZP) is associated with increased alpha-amino-3-hydroxy-5-methylisoxasole-4-propionic acid (AMPA) receptor (AMPAR) miniature excitatory postsynaptic currents (mEPSCs) but reduction of N-methyl-D-aspartic acid (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, intraperitoneal) at withdrawal onset, strengthening the hypothesis that CA1 neuron AMPAR-mediated hyperexcitability is a central component of a functional anatomic circuit associated with the 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, negative-feedback role to prevent AMPAR-mediated neuronal overexcitation. NMDAR antagonist administration (MK-801, 0.25 mg/kg intraperitoneally) had no effect on modifying increased glutamatergic strength or on withdrawal anxiety, whereas injection of an L-type voltage-gated calcium channel antagonist, nimodipine (10 mg/kg, intraperitoneally) averted AMPAR current enhancement and anxiety-like behavior, suggesting that these manifestations may be initiated by a voltage-gated calcium channel-dependent 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. SN - 0955-8810 UR - https://www.unboundmedicine.com/medline/citation/17762513/Benzodiazepine_induced_hippocampal_CA1_neuron_alpha_amino_3_hydroxy_5_methylisoxasole_4_propionic_acid__AMPA__receptor_plasticity_linked_to_severity_of_withdrawal_anxiety:_differential_role_of_voltage_gated_calcium_channels_and_N_methyl_D_aspartic_acid_receptors_ L2 - https://doi.org/10.1097/FBP.0b013e3282d28f2b DB - PRIME DP - Unbound Medicine ER -

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