Brabant Christian, Quertemont Etienne, Anaclet Christelle, Lin Jian-Sheng, Ohtsu Hiroshi, Tirelli Ezio
Unité de Recherche en Psychologie Expérimentale et en Neurosciences Cognitives (URPENC), Université de Liège, Boulevard du Rectorat, B-32, 4000, Liège, Belgium.
Psychopharmacology (Berl). 2007 Feb;190(2):251-63. doi: 10.1007/s00213-006-0603-0. Epub 2006 Oct 28.
Lesion studies have shown that the tuberomammillary nucleus (TM) exerts inhibitory effects on the brain reward system. To determine whether histamine from the TM is involved in that reward inhibitory function, we assessed the stimulant and rewarding effects of cocaine in knockout mice lacking histidine decarboxylase (HDC KO mice), the histamine-synthesizing enzyme. If histamine actually plays an inhibitory role in reward, then it would be expected that mice lacking histamine would be more sensitive to the behavioral effects of cocaine.
The first experiment characterized spontaneous locomotion and cocaine-induced hyperactivity (0, 8, and 16 mg/kg, i.p.) in wild-type and HDC KO mice. The rewarding effects of cocaine were investigated in a second experiment with the place-conditioning technique.
The first experiment demonstrated that histidine decarboxylase mice showed reduced exploratory behaviors but normal habituation to the test chambers. After habituation to the test chambers, HDC KO mice were slightly, but significantly, less stimulated by cocaine than control mice. This finding was replicated in the second experiment, when cocaine-induced activity was monitored with the place-conditioning apparatus. Furthermore, a significant place preference was present in both genotypes for 8 and 16 mg/kg cocaine, but not for 2 and 4 mg/kg.
Our data confirm previous results demonstrating that HDC KO mice show reduced exploratory behaviors. However, contrary to the hypothesis that histamine plays an inhibitory role in reward, histamine-deficient mice were not more responsive to the psychostimulant effects of cocaine.
病变研究表明，结节乳头体核（TM）对大脑奖赏系统具有抑制作用。为了确定来自TM的组胺是否参与该奖赏抑制功能，我们评估了缺乏组胺合成酶组氨酸脱羧酶的基因敲除小鼠（HDC基因敲除小鼠）对可卡因的刺激和奖赏作用。如果组胺在奖赏中确实起抑制作用，那么预计缺乏组胺的小鼠对可卡因的行为效应会更敏感。
第一个实验对野生型和HDC基因敲除小鼠的自发运动和可卡因诱导的多动（0、8和16mg/kg，腹腔注射）进行了表征。在第二个实验中，采用位置条件反射技术研究了可卡因的奖赏作用。
第一个实验表明，组氨酸脱羧酶小鼠的探索行为减少，但对测试箱的习惯化正常。在适应测试箱后，HDC基因敲除小鼠受到可卡因的刺激比对照小鼠略少，但差异显著。当用位置条件反射装置监测可卡因诱导的活动时，这一发现在第二个实验中得到了重复。此外，两种基因型的小鼠对8mg/kg和16mg/kg的可卡因均表现出显著的位置偏爱，但对2mg/kg和4mg/kg的可卡因则没有。
我们的数据证实了先前的结果，即HDC基因敲除小鼠的探索行为减少。然而，与组胺在奖赏中起抑制作用的假设相反，缺乏组胺的小鼠对可卡因的精神刺激作用并没有更敏感。
