Hippocampal-Dependent Antidepressant Action of the H3 Receptor Antagonist Clobenpropit in a Rat Model of Depression

The International Journal of Neuropsychopharmacology
Teresa FemeníaMaria Lindskog

Abstract

Histamine is a modulatory neurotransmitter regulating neuronal activity. Antidepressant drugs target modulatory neurotransmitters, thus ultimately regulating glutamatergic transmission and plasticity. Histamine H3 receptor (H3R) antagonists have both pro-cognitive and antidepressant effects; however, the mechanism by which they modulate glutamate transmission is not clear. We measured the effects of the H3R antagonist clobenpropit in the Flinders Sensitive Line (FSL), a rat model of depression with impaired memory and altered glutamatergic transmission. Behavioral tests included the forced swim test, memory tasks (passive avoidance, novel object recognition tests), and anxiety-related paradigms (novelty suppressed feeding, social interaction, light/dark box tests). Hippocampal protein levels were detected by Western blot. Hippocampal plasticity was studied by in slice field recording of CA3-CA1 long-term synaptic potentiation (LTP), and glutamatergic transmission by whole-cell patch clamp recording of excitatory postsynaptic currents (EPSCs) in CA1 pyramidal neurons. Clobenpropit, administered systemically or directly into the hippocampus, decreased immobility during the forced swim test; systemic injections reversed memory def...Continue Reading

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Citations

May 9, 2015·Frontiers in Behavioral Neuroscience·Salvatore MagaraMaria Lindskog
Dec 3, 2016·Neuropharmacology·Maria Domenica SannaNicoletta Galeotti
Jun 10, 2017·Expert Review of Neurotherapeutics·Gopalkumar RakeshPrakash S Masand
Aug 22, 2018·British Journal of Pharmacology·Gustavo ProvensiMaria Beatrice Passani
Sep 9, 2017·The World Journal of Biological Psychiatry : the Official Journal of the World Federation of Societies of Biological Psychiatry·Thomas DemuyserIlse Smolders
Jun 28, 2018·Frontiers in Physiology·María E Riveros, Mauricio A Retamal

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Methods Mentioned

BETA
dissection

Software Mentioned

JMP11
Mini Analysis
GraphPad Prism
EthoVision
AxoGraph X
ImageJ
GraphPad

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