Acetaminophen differentially enhances social behavior and cortical cannabinoid levels in inbred mice.
Acetaminophen differentially enhances social behavior and cortical cannabinoid levels in inbred mice.
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DOI：
10.1016/j.pnpbp.2012.04.011
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发表时间：
2012-08-07
影响因子：
5.6
通讯作者：
Schultz, Stephen T.
中科院分区：
文献类型：
--
作者：
Gould, Georgianna G.;Seillier, Alexandre;Weiss, Gabriela;Giuffrida, Andrea;Burke, Teresa F.;Hensler, Julie G.;Rock, Crystal;Tristan, Amanda;McMahon, Lance R.;Salazar, Alexander;O'Connor, Jason C.;Satsangi, Neera;Satsangi, Rajiv K.;Gu, Ting-Ting;Treat, Keenan;Smolik, Corey;Schultz, Stephen T.
据报道，超治疗剂量的止痛剂对乙酰氨基酚（paracetomol）可以促进瑞士小鼠的社会行为。然而，我们假设，它可能不会促进社交在其他菌株由于大麻素CB 1受体介导的抑制5-羟色胺（5-HT）在额叶皮层的传输。我们在两种社交缺陷小鼠品系BTBR和129 S1/SvImJ（129 S）中研究了对乙酰氨基酚对社交和重复行为的影响，并与大麻素激动剂WIN 55，212 -2进行了比较。对乙酰氨基酚（100 mg/kg）在血清浓度≥70 ng/ml时增强BTBR中的社会互动，以及129 S中的社会新奇偏好和大理石埋葬。在注射对乙酰氨基酚或进行社交测试后，BTBR额叶皮质中的花生四烯酸（AEA）增加，而行为测试增加了129 S额叶皮质中的2-花生四烯酸甘油（2-AG）水平。相比之下，WIN 55，212 -2（0.1 mg/kg）没有增强社交能力。此外，我们预计CB 1缺陷（+/−）小鼠的社会性低于野生型，但却发现了类似的社会性。由于内源性大麻素对对乙酰氨基酚反应的菌株差异，我们比较了皮质CB 1和5-HT 1A受体密度和功能相对于社交C57 BL/6小鼠。在不同品系的额叶皮质中，CB 1受体饱和结合（Bmax= 958±117 fmol/mg蛋白）和对[3 H] CP 55，940的亲和力（KD= 3±0.8 nM）相似。在BTBR、129 S和C57 BL/6小鼠中，CP 55，940刺激的扣带回皮质中的[35 S]GTPγS结合分别比基础值高136±12、156±22和75±9%。对乙酰氨基酚代谢产物对氨基苯酚（1μM）未能刺激[35 S]GTPγS结合。因此，似乎对乙酰氨基酚的其他间接作用，包括5-HT受体激动，可能是其社交促进特性的基础，超过了这些小鼠中局部升高的内源性大麻素引起的任何CB 1介导的抑制。
Supratherapeutic doses of the analgesic acetaminophen (paracetomol) are reported to promote social behavior in Swiss mice. However, we hypothesized that it might not promote sociability in other strains due to cannabinoid CB1 receptor-mediated inhibition of serotonin (5-HT) transmission in the frontal cortex. We examined the effects of acetaminophen on social and repetitive behaviors in comparison to a cannabinoid agonist, WIN 55,212-2, in two strains of socially-deficient mice, BTBR and 129S1/SvImJ (129S). Acetaminophen (100 mg/kg) enhanced social interactions in BTBR, and social novelty preference and marble burying in 129S at serum levels ≥70 ng/ml. Following acetaminophen injection or sociability testing, anandamide (AEA) increased in BTBR frontal cortex, while behavior testing increased 2-arachidonyl glycerol (2-AG) levels in 129S frontal cortex. In contrast, WIN 55,212-2 (0.1 mg/kg) did not enhance sociability. Further, we expected CB1-deficient (+/−) mice to be less social than wild-type, but instead found similar sociability. Given strain differences in endocannabinoid response to acetaminophen, we compared cortical CB1 and 5-HT1A receptor density and function relative to sociable C57BL/6 mice. CB1 receptor saturation binding (Bmax= 958±117 fmol/mg protein), and affinity for [3H]CP55,940 (KD= 3±0.8 nM) was similar in frontal cortex among strains. CP55,940-stimulated [35S]GTPγS binding in cingulate cortex was 136±12, 156±22, and 75±9% above basal in BTBR, 129S and C57BL/6 mice. The acetaminophen metabolite para-aminophenol (1μM) failed to stimulate [35S]GTPγS binding. Hence, it appears that other indirect actions of acetaminophen, including 5-HT receptor agonism, may underlie its sociability promoting properties outweighing any CB1 mediated suppression by locally-elevated endocannabinoids in these mice.
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影响因子：
2
作者：
Derntl B;Seidel EM;Eickhoff SB;Kellermann T;Gur RC;Schneider F;Habel U
通讯作者：
Habel U
影响因子：
2.7
作者：
Boylan, Carolyn B.;Blue, Mary E.;Hohmann, Christine F.
通讯作者：
Hohmann, Christine F.
影响因子：
4.3
作者：
Bartolomucci, Alessandro;Carola, Valeria;Gross, Cornelius
通讯作者：
Gross, Cornelius
影响因子：
2.8
作者：
Filipenko, ML;Beilina, AG;Kudryavtseva, NN
通讯作者：
Kudryavtseva, NN
影响因子：
5.3
作者：
Baliki, Marwan N.;Chialvo, Dante R.;Apkarian, A. Vania
通讯作者：
Apkarian, A. Vania