EFFECTS OF ?-FLUOROMETHYLHISTIDINE,AN IRREVERSIBLE INHIBITOR OF HISTIDINE DECARBOXYLASE,ON TURNING BEHAVIOR AND DOPANERGIC AND HISTAMINERGIC NEURONS IN 6-HYDROXYDOPAMINE-LESIONED RATS / 解剖学报

ABSTRACT

Objective To investigate the role of endogenous histamine in Parkinson disease. Methods 6-OHDA-lesioned rats were prepared by the conventional mothod,and in the meantime a group of rats were administrated with ?-fluoromethylhistidine(?-FMH),an irreversible inhibitor of histidine decarboxylase(HDC),via intracerebroventricular injection(12.5 ?g or 25 ?g,i.c.v.) for seven days.On the 7 day,the apomorphine-induced turning behavior and were detected, and the immunoreactivity of dopaminergic neurons in the substantia nigra pars compact(SNc) and histaminergic neurons in the tuberomammillary nucleus(TMN) were evaluated by tyrosine hydroxylase(TH) and HDC immunohistochemistry,respectively.Additionally,the level of dopamine in striatum was determined with high performance liquid chromatography(HPLC). Results ?-FMH(25 ?g,i.c.v.) significantly reduced the turning behavior and prevented the loss of dopaminergic neurons in the SNc,and slightly increased dopamine level in the striatum.Whereas,the immunoreactivity of histaminergic neurons in the TMN of hypothalamus in both the 6-OHDA lesioned and the ?-FMH treated rats was not changed.Conclusion Endogeneous histamine may involve in the pathological processes of PD.However,the histaminergic neurons are not involved in PD.