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Increased brain histamine in an alcohol‐preferring rat line, and modulation of ethanol consumption by H 3 receptor mechanisms
Author(s) -
Lintunen Minnamaija,
Hyytiä Petri,
Sallmen Tina,
Karlstedt Kaj,
Tuomisto Leena,
Leurs Rob,
Kiianmaa Kalervo,
Korpi Esa R.,
Panula Pertti
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fsb2fj000545fje
Subject(s) - histaminergic , thioperamide , histamine h3 receptor , histamine , chemistry , agonist , histamine h2 receptor , pharmacology , endocrinology , receptor , histamine h1 receptor , ethanol , medicine , biochemistry , antagonist , biology
The histaminergic system is thought to regulate brain reward, but the exact mechanisms are poorly understood. This study aims to reveal the pathophysiological differences in the brain histaminergic system between selectively outbred alcohol‐preferring AA and alcohol‐avoiding ANA rats by using a combination of biochemical, immunohistochemical, and molecular biological methods. We also want to test the functional significance of the system by using operant ethanol self‐administration method. We show that alcohol‐preferring AA rats, when compared with alcohol‐avoiding ANA rats, display higher levels of brain histamine and its first metabolite as measured by HPLC and mass spectrometry, a higher density of histamine‐immunoreactive nerve fibers, and lower H 1 receptor mRNA expression and H 1 and H 3 receptor binding as studied by using in situ hybridization and autoradiography. Two H 3 receptor antagonists, thioperamide and clobenpropit, reduced and an agonist, R‐α‐methylhistamine, increased operant responding for ethanol by the alcohol‐preferring rats, whereas an H 1 receptor ligand, mepyramine, was inefficient. The results indicate that high alcohol preference is correlated with enhanced histaminergic mechanisms, most likely via H 3 receptor‐mediated processes. Central histaminergic mechanisms may thus participate also in other addictive behaviors.