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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

N-methyl-D-aspartate receptor antagonists enhance histamine neuron activity in rodent brain.

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 (ED50 of approximately 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 H3-receptor antagonist/inverse agonists for the symptomatic treatment of schizophrenia.[1]


  1. N-methyl-D-aspartate receptor antagonists enhance histamine neuron activity in rodent brain. Faucard, R., Armand, V., Héron, A., Cochois, V., Schwartz, J.C., Arrang, J.M. J. Neurochem. (2006) [Pubmed]
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