JPET # 170928 1 Histamine and H 3 receptor in alcohol - related behaviors

Data from rat models for alcohol preference and histidine decarboxylase knockout (HDC KO) mice suggest that brain histamine regulates alcohol-related behaviors. Histamine levels are higher in alcoholpreferring than alcohol non-preferring rat brains, and expression of histamine H3 receptor is different in key areas for addictive behavior. Histamine H3 receptor inverse agonists decrease alcohol responding in one alcohol-preferring rat line. Conditioned place preference induced by alcohol is stronger in HDC KO mice than control mice. The HDC KO mice display a weaker stimulatory response to acute alcohol than the wild type (WT) mice. In male inbred C57BL/6 mice H3 receptor antagonist ciproxifan inhibits the ethanol-evoked stimulation of locomotor activity. Ciproxifan also potentiates the ethanol reward, , but does not alone result in the development of place preference. At least in one rat model developed to study alcohol sensitivity, high histamine levels are characteristic of the alcohol insensitive rat line, and lowering brain histamine with a HDC inhibitor increases alcohol sensitivity in the tilting plane test. However, the motor skills of HDC KO mice do not appear to differ from those of the WT mice. Current evidence suggests that the histaminergic system is involved in regulation of place preference behavior triggered by alcohol, possibly through an interaction with the mesolimbic dopamine system. Histamine may also interact with dopamine in regulation of the cortico-striato-pallido-thalamo-cortical motor pathway and cerebellar mechanisms, which may be important in different motor behaviors beyond alcohol-induced motor disturbances. Histamine H3 receptor ligands may have significant effects on alcohol addiction. This article has not been copyedited and formatted. The final version may differ from this version. JPET Fast Forward. Published on September 23, 2010 as DOI: 10.1124/jpet.110.170928 at A PE T Jornals on Sptem er 3, 2017 jpet.asjournals.org D ow nladed from