大麻和其中富含的主要精神类成分THC（四氢大麻酚）能使人类和动物产生过度的行为作用。其中的一些作用是造成目前大麻大量违法使用的原因，而另外一些则可能被用于治疗某些神经异常的疾病。
THC产生的绝大部分作用是由大麻素受体1（CB1）引起的，这种受体在中枢神经系统中得到广泛表达。但是在这之前，其行为的精确解剖学和神经学本质并不清楚。
利用一种先进的基因分析方法，来自德国Mainz的JohannesGutenberg大学的Kristina Monory和她的同事发现了是特殊的神经组分造成了THC的以上独特作用。他们的研究结果发表在本周的在线版刊物PLoS Biology上。
在研究中，科学家利用了一种基因变异的老鼠，该老鼠在特定的神经组分中缺少CB1表达，而在其它神经组分中则正常。然后科学家用THC处理这些老鼠，接着评估药物引起的典型行为：运动、疼痛、热感等。他们获得的引起THC特殊作用的神经本质能精确解释大麻化学成分的药理学作用。更重要的是这些数据提供的原理能帮助制造选择性激发特定神经组分中CB1的药物，从而更好的利用大麻化学成分进行医学治疗。(教育部科技发展中心)
原文链接：http://www.physorg.com/news111129321.html
原始出处：
PLoS Biology
Received: February 21, 2007; Accepted: August 14, 2007; Published: October 9, 2007
Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice
Krisztina Monory1,2, Heike Blaudzun2, Federico Massa1,2, Nadine Kaiser1, Thomas Lemberger3, Günther Schütz3, Carsten T. Wotjak2, Beat Lutz1,2*, Giovanni Marsicano1,4*
1 Department of Physiological Chemistry, Johannes Gutenberg University Mainz, Mainz, Germany, 2 Max Planck Institute of Psychiatry, Munich, Germany, 3 Department of Molecular Biology of the Cell I, German Cancer Research Center, Heidelberg, Germany, 4 U862 Institute F. Magendie, University Bordeaux 2, INSERM, Avenir Group 4, Bordeaux, France
Marijuana and its main psychotropic ingredient Δ9-tetrahydrocannabinol (THC) exert a plethora of psychoactive effects through the activation of the neuronal cannabinoid receptor type 1 (CB1), which is expressed by different neuronal subpopulations in the central nervous system. The exact neuroanatomical substrates underlying each effect of THC are, however, not known. We tested locomotor, hypothermic, analgesic, and cataleptic effects of THC in conditional knockout mouse lines, which lack the expression of CB1 in different neuronal subpopulations, including principal brain neurons, GABAergic neurons (those that release γ aminobutyric acid), cortical glutamatergic neurons, and neurons expressing the dopamine receptor D1, respectively. Surprisingly, mice lacking CB1 in GABAergic neurons responded to THC similarly as wild-type littermates did, whereas deletion of the receptor in all principal neurons abolished or strongly reduced the behavioural and autonomic responses to the drug. Moreover, locomotor and hypothermic effects of THC depend on cortical glutamatergic neurons, whereas the deletion of CB1 from the majority of striatal neurons and a subpopulation of cortical glutamatergic neurons blocked the cataleptic effect of the drug. These data show that several important pharmacological actions of THC do not depend on functional expression of CB1 on GABAergic interneurons, but on other neuronal populations, and pave the way to a refined interpretation of the pharmacological effects of cannabinoids on neuronal functions.
Figure 1. Hypolocomotor, Hypothermic, Analgesic, and Cataleptic Effects of THC Depend on CB1 Receptors
(A–D) Dose-response of THC effects in wild-type mice. Effects of vehicle (n = 16), 1 mg/kg (n = 9), 3 mg/kg (n = 9), and 10 mg/kg THC (n = 10), respectively, on the “tetrad” battery of tests consisting of (A) locomotor, (B) hypothermic, (C) analgesic, and (D) cataleptic effects. (E–H) THC effects depend on CB1 receptor. Wild-type CB1+/+ and littermate CB1−/− mice (i.e., null CB1 mutants) were tested for (E) locomotor, (F) hypothermic, (C) analgesic, and (D) cataleptic effects of 10 mg/kg THC. Note the absence of any effect of the drug in CB1−/−. #, ##, ###; p < 0.05, p < 0.01, p < 0.001, respectively, as compared to vehicle-treated animals (two-way ANOVA, followed by Dunnet's post-hoc test). ***, p < 0.001 (two-way ANOVA, followed by Newman-Keuls post-hoc test).
全文链接：http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050269
