大麻和其中富含的主要精神類成分THC（四氫大麻酚）能使人類和動(dòng)物產(chǎn)生過(guò)度的行為作用,。其中的一些作用是造成目前大麻大量違法使用的原因，而另外一些則可能被用于治療某些神經(jīng)異常的疾病,。
THC產(chǎn)生的絕大部分作用是由大麻素受體1（CB1）引起的,，這種受體在中樞神經(jīng)系統(tǒng)中得到廣泛表達(dá)。但是在這之前,，其行為的精確解剖學(xué)和神經(jīng)學(xué)本質(zhì)并不清楚,。
利用一種先進(jìn)的基因分析方法，來(lái)自德國(guó)Mainz的JohannesGutenberg大學(xué)的Kristina Monory和她的同事發(fā)現(xiàn)了是特殊的神經(jīng)組分造成了THC的以上獨(dú)特作用,。他們的研究結(jié)果發(fā)表在本周的在線版刊物PLoS Biology上,。
在研究中，科學(xué)家利用了一種基因變異的老鼠，該老鼠在特定的神經(jīng)組分中缺少CB1表達(dá),，而在其它神經(jīng)組分中則正常,。然后科學(xué)家用THC處理這些老鼠，接著評(píng)估藥物引起的典型行為：運(yùn)動(dòng),、疼痛,、熱感等。他們獲得的引起THC特殊作用的神經(jīng)本質(zhì)能精確解釋大麻化學(xué)成分的藥理學(xué)作用,。更重要的是這些數(shù)據(jù)提供的原理能幫助制造選擇性激發(fā)特定神經(jīng)組分中CB1的藥物,，從而更好的利用大麻化學(xué)成分進(jìn)行醫(yī)學(xué)治療。(教育部科技發(fā)展中心)
原文鏈接：http://www.physorg.com/news111129321.html
原始出處：
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).
全文鏈接：http://biology.plosjournals.org/perlserv/?request=get-document&doi=10.1371/journal.pbio.0050269
