Endogenous histamine inhibits the development of morphine-induced conditioned place preference  

作　　者：Ying-xia GONG Min LV Yong-ping ZHU Yuan-yuan ZHU Er-qing WEI Hong SHI Qun-li ZENG Zhong CHEN 

机构地区：[1]Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310031, China [2]Department of Pharmacology, Zhejiang Academy of Medical Sciences, Hangzhou 310031, China

出　　处：《Acta Pharmacologica Sinica》2007年第1期10-18,共9页中国药理学报（英文版）

基　　金：a National Rasic Research of China grant (No_ 2003CB515400);National Natural Science Foundation of China grants(No_ 30371638, 30472013 and 30572176);the Zhejiang Provincial Natural Science Foundation of China (No 8303779)

摘　　要：Aim： The conditioned place preference （CPP） paradigm was used to investigate the effects of endogenous histamine on the processes leading to morphineinduced reward-seeking behavior in Sprague-Dawley rats. Methods： The model of CPP was used to assess the rewarding effect of morphine. The levels of histamine, glutamate, γ-aminobutyric acid （GABA）, dopamine （DA） and 3, 4-dihydroxyphenylacetic acid （DOPAC） in rat brains were measured with high-performance liquid chromatography. Immunohistochemistry technique was used to observe the morphological changes of neurons. Results： Intraperitoneal injection of morphine （2, 5 or 10 mg/kg） induced the development of CPP in a dose-dependent manner. In addition, morphine administrations （10 mg/kg） decreased the histamine content and reduced the number and size of histaminergic neurons in the tuberomammillary nucleus （TM）, as well as markedly increasing the DOPAC/DA ratios in the ventral tegmental area （VTA） and nucleus accumbens （NAc）. Intraperitoneal injection of histidine （50, 100 or 200 mg/kg） dose-dependently inhibited the development of morphine-induced CPP. Bilateral lesions of the TM, which decreased the histamine levels in the VTA and NAc, potentiated the development of CPP induced by morphine （1 mg/kg, a dose that produced no appreciable effect when given alone） and increased the DOPAC/DA ratios in the VTA and NAc, but did not change the glutamate or GABA levels in these nuclei. Histidine reversed the effects of the TM lesions. Conclusion： These results indicate that endogenous histamine plays a role in inhibiting the development of morphine-induced reward-seeking behavior, and the inhibition may involve the modulation of dopaminergic activity.Aim： The conditioned place preference （CPP） paradigm was used to investigate the effects of endogenous histamine on the processes leading to morphineinduced reward-seeking behavior in Sprague-Dawley rats. Methods： The model of CPP was used to assess the rewarding effect of morphine. The levels of histamine, glutamate, γ-aminobutyric acid （GABA）, dopamine （DA） and 3, 4-dihydroxyphenylacetic acid （DOPAC） in rat brains were measured with high-performance liquid chromatography. Immunohistochemistry technique was used to observe the morphological changes of neurons. Results： Intraperitoneal injection of morphine （2, 5 or 10 mg/kg） induced the development of CPP in a dose-dependent manner. In addition, morphine administrations （10 mg/kg） decreased the histamine content and reduced the number and size of histaminergic neurons in the tuberomammillary nucleus （TM）, as well as markedly increasing the DOPAC/DA ratios in the ventral tegmental area （VTA） and nucleus accumbens （NAc）. Intraperitoneal injection of histidine （50, 100 or 200 mg/kg） dose-dependently inhibited the development of morphine-induced CPP. Bilateral lesions of the TM, which decreased the histamine levels in the VTA and NAc, potentiated the development of CPP induced by morphine （1 mg/kg, a dose that produced no appreciable effect when given alone） and increased the DOPAC/DA ratios in the VTA and NAc, but did not change the glutamate or GABA levels in these nuclei. Histidine reversed the effects of the TM lesions. Conclusion： These results indicate that endogenous histamine plays a role in inhibiting the development of morphine-induced reward-seeking behavior, and the inhibition may involve the modulation of dopaminergic activity.

关 键 词：conditioned place preference HISTAMINE MORPHINE RAT tuberomammillary nucleus 

分 类 号：R656.4[医药卫生—外科学]