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Benzodiazepine inhibits hypothalamic presympathetic neurons by potentiation of GABAergic synaptic input.
Neuropharmacology. 2007 Feb; 52(2):467-75.N

Abstract

Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus receive inputs from gamma-aminobutyric acid (GABA)-containing neurons, which regulate sympathetic outflow and cardiovascular function. Benzodiazepines can decrease blood pressure and sympathetic nerve activity when used for induction of anesthesia, but the sites and mechanisms of action are uncertain. In this study, we determined the effect of the benzodiazepine agonist diazepam on GABAergic inhibitory postsynaptic currents (IPSCs) and the firing activity of rostral ventrolateral medulla (RVLM)-projecting PVN neurons. RVLM-projecting PVN neurons were retrogradely labeled by fluorescent microspheres injected into the RVLM in rats. Whole-cell and cell-attached recordings were performed on labeled PVN neurons in the hypothalamic brain slice. Bath application of 1-10 microM diazepam significantly increased the decay time constants of the GABAergic miniature IPSCs and evoked IPSCs in a dose-dependent manner. Also, diazepam significantly increased the amplitude of evoked IPSCs but not of miniature IPSCs. Pretreatment with the benzodiazepine antagonist flumazenil completely blocked the diazepam-induced increases in the amplitude and decay time constants of the evoked IPSCs. Furthermore, diazepam significantly decreased the firing activity of PVN-RVLM neurons that responded with increased firing to the GABA(A) receptor antagonist bicuculline. In contrast, diazepam had no significant effect on the firing activity of bicuculline-unresponsive PVN-RVLM neurons. This study provides new information that the benzodiazepine suppresses the firing activity of PVN presympathetic neurons by potentiation of GABAergic inputs.

Authors+Show Affiliations

Department of Anesthesiology, Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17045312

Citation

Zahner, Matthew R., et al. "Benzodiazepine Inhibits Hypothalamic Presympathetic Neurons By Potentiation of GABAergic Synaptic Input." Neuropharmacology, vol. 52, no. 2, 2007, pp. 467-75.
Zahner MR, Li DP, Pan HL. Benzodiazepine inhibits hypothalamic presympathetic neurons by potentiation of GABAergic synaptic input. Neuropharmacology. 2007;52(2):467-75.
Zahner, M. R., Li, D. P., & Pan, H. L. (2007). Benzodiazepine inhibits hypothalamic presympathetic neurons by potentiation of GABAergic synaptic input. Neuropharmacology, 52(2), 467-75.
Zahner MR, Li DP, Pan HL. Benzodiazepine Inhibits Hypothalamic Presympathetic Neurons By Potentiation of GABAergic Synaptic Input. Neuropharmacology. 2007;52(2):467-75. PubMed PMID: 17045312.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Benzodiazepine inhibits hypothalamic presympathetic neurons by potentiation of GABAergic synaptic input. AU - Zahner,Matthew R, AU - Li,De-Pei, AU - Pan,Hui-Lin, Y1 - 2006/10/10/ PY - 2006/07/20/received PY - 2006/08/15/revised PY - 2006/08/17/accepted PY - 2006/10/19/pubmed PY - 2007/4/11/medline PY - 2006/10/19/entrez SP - 467 EP - 75 JF - Neuropharmacology JO - Neuropharmacology VL - 52 IS - 2 N2 - Presympathetic neurons in the paraventricular nucleus (PVN) of the hypothalamus receive inputs from gamma-aminobutyric acid (GABA)-containing neurons, which regulate sympathetic outflow and cardiovascular function. Benzodiazepines can decrease blood pressure and sympathetic nerve activity when used for induction of anesthesia, but the sites and mechanisms of action are uncertain. In this study, we determined the effect of the benzodiazepine agonist diazepam on GABAergic inhibitory postsynaptic currents (IPSCs) and the firing activity of rostral ventrolateral medulla (RVLM)-projecting PVN neurons. RVLM-projecting PVN neurons were retrogradely labeled by fluorescent microspheres injected into the RVLM in rats. Whole-cell and cell-attached recordings were performed on labeled PVN neurons in the hypothalamic brain slice. Bath application of 1-10 microM diazepam significantly increased the decay time constants of the GABAergic miniature IPSCs and evoked IPSCs in a dose-dependent manner. Also, diazepam significantly increased the amplitude of evoked IPSCs but not of miniature IPSCs. Pretreatment with the benzodiazepine antagonist flumazenil completely blocked the diazepam-induced increases in the amplitude and decay time constants of the evoked IPSCs. Furthermore, diazepam significantly decreased the firing activity of PVN-RVLM neurons that responded with increased firing to the GABA(A) receptor antagonist bicuculline. In contrast, diazepam had no significant effect on the firing activity of bicuculline-unresponsive PVN-RVLM neurons. This study provides new information that the benzodiazepine suppresses the firing activity of PVN presympathetic neurons by potentiation of GABAergic inputs. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/17045312/Benzodiazepine_inhibits_hypothalamic_presympathetic_neurons_by_potentiation_of_GABAergic_synaptic_input_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(06)00287-5 DB - PRIME DP - Unbound Medicine ER -