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Evidence for activation of histamine H 3 autoreceptors during handling stress in the prefrontal cortex of the rat
Author(s) -
Westerink Ben H.C.,
Cremers Thomas I.F.H.,
De Vries Jan B.,
Liefers Hans,
Tran Nan,
De Boer Peter
Publication year - 2002
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.10043
Subject(s) - thioperamide , microdialysis , autoreceptor , histamine , histamine h3 receptor , chemistry , tetrodotoxin , agonist , histaminergic , antagonist , medicine , pharmacology , endocrinology , receptor , extracellular , biochemistry , biology
On‐line microdialysis of histamine in 10‐min samples of the prefrontal cortex of the conscious rat is described. The HPLC‐fluorescent assay for histamine in dialysates has been significantly simplified by using only one postcolumn reagent line instead of the three reagent lines described in earlier methods. The method is selective, sensitive (detection limit: 2–3 fmol on column), and linear over a large concentration range. Basal values of histamine decreased to about 50% of basal levels during infusion of tetrodotoxin (5 × 10 ‐6 M). Handling rats for 15 min increased histamine in dialysates to about 300% of basal levels. When tetrodotoxin (10 ‐6 M) was applied during handling the increase in histamine release was strongly (about 80%) suppressed. The handling‐induced increase in histamine was used as a paradigm to investigate the functional activity of histamine H 3 autoreceptors during mild stress or arousal. An H 3 receptor specific agonist (α‐methylhistamine; 10 ‐5 M) and antagonist (thioperamide; 10 ‐5 M) were infused into the frontal cortex via the microdialysis probe. The effect of handling on histamine release was potentiated during infusion of thioperamide and fully suppressed during infusion of α‐methylhistamine. These results clearly illustrate the efficacy of the H 3 autoreceptor in modulating stimulated histamine release during natural stimulatory conditions. Synapse 43:238–243, 2002. © 2002 Wiley‐Liss, Inc.