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N ‐methyl‐ d ‐aspartate receptor antagonists enhance histamine neuron activity in rodent brain
Author(s) -
Faucard Raphaël,
Armand Vincent,
Héron Anne,
Cochois Véronique,
Schwartz JeanCharles,
Arrang JeanMichel
Publication year - 2006
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.1471-4159.2006.04002.x
Subject(s) - histaminergic , nmda receptor , histamine h3 receptor , ifenprodil , phencyclidine , medicine , nucleus accumbens , chemistry , glutamate receptor , histidine decarboxylase , endocrinology , histamine h1 receptor , histamine , biology , pharmacology , receptor , agonist , antagonist , central nervous system , biochemistry , amino acid , histidine
The modulation of histamine neuron activity by various non‐competitive NMDA‐receptor antagonists was evaluated by changes in tele ‐methylhistamine ( t ‐MeHA) levels and histidine decarboxylase ( hdc ) mRNA expression induced in rodent brain. The NMDA open‐channel blockers phencyclidine (PCP) and MK‐801 enhanced t ‐MeHA levels in mouse brain by 50–60%. Ifenprodil, which interacts with polyamine sites of NR2B‐containing NMDA receptors, had no effect. PCP also increased hdc mRNA expression in the rat tuberomammillary nucleus. The enhancement of t ‐MeHA levels elicited by MK‐801 (ED 50 of ∼0.1 mg/kg) was observed in the hypothalamus, cerebral cortex, striatum and hippocampus. Control t ‐MeHA levels and the t ‐MeHA response to MK‐801 were not different in male and female mice. Double immunostaining for HDC and NMDA receptor subunits showed that histamine neurons of the rat tuberomammillary nucleus express NMDA receptor subunit 1 (NR1) with NMDA receptor subunit 2A (NR2A) and NMDA receptor 2B subunit (NR2B). In addition, immunoreactivity for the neuronal glutamate transporter EAAC1 was observed near most histaminergic perikarya. Hence, these findings support the existence of histamine/glutamate functional interactions in the brain. The increase in histamine neuron activity induced by NMDA receptor antagonists further suggests a role of histamine neurons in psychotic disorders. In addition, the decrease in MK‐801‐induced hyperlocomotion observed in mice after administration of ciproxifan further strengthens the potential interest of H 3 ‐receptor antagonist/inverse agonists for the symptomatic treatment of schizophrenia.