Acta Pharmacologica Sinica 2007 January; 28 (1): 10-18; doi 10.1111/j.1745-7254.2007.00470.x

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

Ying-xia GONG2, Min LV2,3, Yong-ping ZHU2, Yuan-yuan ZHU2, Er-qing WEI2, Hong SHI3, Qun-li ZENG2, Zhong CHEN2,4

2Department of Pharmacology and Neurobiology, School of Medicine, Zhejiang University, Hangzhou 310031, China; 3Department of Pharmacology, Zhejiang Academy of Medical Sciences, Hangzhou 310031, China

 

Aim: The conditioned place preference (CPP) paradigm was used to investigatethe effects of endogenous histamine on the processes leading to morphine- induced 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, g-aminobutyric acid (GABA), dopamine (DA) and 3, 4-dihydroxyphenyl-acetic 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). Intra-peritoneal 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 effectwhen 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 dopa-minergic activity.

 

Keywords: conditioned place preference; histamine; morphine; rat; tuberomammillary nucleus

 
1 Project supported by a National Basic Research of China grant (No 2003CB515400), National Natural Science Foundation of China grants (No 30371638, 30472013 and 30572176) and partly supported by the Zhejiang Provincial Natural Science Foundation of China (No R303779).

4 Correspondence to Prof Zhong CHEN.
Phn 86-571-8721-7269.
Fax 86-571-8721-7446.
E-mail chenzhong@zju.edu.cn
Received 2006-07-02     Accepted 2006-08-18

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