Unité Mixte de Recherche-Centre National de la Recherche Scientifique (UMR-CNRS) 5293, Institut des Maladies Neurodégénératives, Université de Bordeaux, 146 rue Léo Saignat, B.P.281, 33076 Bordeaux Cedex, France.
Eur J Pharmacol. 2012 Aug 15;689(1-3):8-16. doi: 10.1016/j.ejphar.2012.05.022. Epub 2012 May 27.
Serotonin(2C) receptors (5-HT(2)C) exert continuous control on the activity of specific populations of neurons in the basal ganglia. While antagonists block the effect of endogenous 5-HT at 5-HT(2C) receptors, the actions of inverse agonists may also involve interruption of activity at constitutively active populations of 5-HT(2C) receptors. We have evaluated the regional impact of these controls by studying, in rats, the expression of the product of the proto-oncogene c-Fos in rat basal ganglia after peripheral doses of the 5-HT(2C) antagonist SB 243213 (5-methyl-1-[[2-[(2-methyl-3-pyridyl)oxy]-5-pyridyl]carbamoyl]-6-trifluoromethylindoline) and the 5-HT(2B/2C) inverse agonists SB 206553 (5-methyl-1-(3-pyridylcarbamoyl)-1,2,3,5-tetrahydropyrrolo[2,3-f]indole.hydrochloride) and S32006 (N-pyridin-3-yl-1,2-dihydro-3H-benzo[e]indole-3-carboxamide). The results show that 1 and 10mg/kg SB 243213 enhanced equally c-Fos expression in the subthalamic nucleus (STN) and dose-dependently in the striatum and nucleus accumbens core (NAcc). SB 206553 (1-10mg/kg), at 10mg/kg only, enhanced c-Fos expression in STN, striatum (except the dorsomedial part), NAcc, entopeduncular nucleus, substantia nigra pars reticulata (SNr) and compacta (SNc) and ventral tegmental area. S32006 induced a similar increase in c-Fos expression in the medial parts of the striatum and NAcc at doses of 1-10mg/kg while it dose-dependently enhanced c-Fos expression in medial parts of the STN and SNr. None of these drugs induced c-Fos expression in the globus pallidus. The distinct pattern of c-Fos expression elicited by the 5-HT(2C) antagonist and inverse agonists suggests the existence of cellular and functional heterogeneity in the response of the basal ganglia to drugs inhibiting 5-HT(2C) receptors.
血清素（2C）受体（5-HT（2C））对基底神经节中特定神经元群体的活动持续发挥控制作用。虽然拮抗剂阻断内源性 5-HT 在 5-HT（2C）受体上的作用，但反向激动剂的作用也可能涉及到对组成性激活的 5-HT（2C）受体群体的活动的中断。我们通过研究外周给予 5-HT（2C）拮抗剂 SB 243213（5-甲基-1-[[2-（2-甲基-3-吡啶基）氧基]-5-吡啶基]氨基甲酰基]-6-三氟甲基吲哚）和 5-HT（2B/2C）反向激动剂 SB 206553（5-甲基-1-（3-吡啶基氨基甲酰基）-1,2,3,5-四氢吡咯并[2,3-f]吲哚盐酸盐）和 S32006（N-吡啶-3-基-1,2-二氢-3H-苯并[e]吲哚-3-甲酰胺）后，在大鼠基底神经节中，研究原癌基因 c-Fos 产物的表达，评估了这些控制的区域性影响。结果表明，1 和 10mg/kg 的 SB 243213 同样增强了亚丘脑核（STN）和纹状体和伏隔核核心（NAcc）中的 c-Fos 表达，且呈剂量依赖性。SB 206553（1-10mg/kg），仅在 10mg/kg 时，增强了 STN、纹状体（除背侧部分外）、NAcc、脚间核、黑质网状部（SNr）和致密部（SNc）和腹侧被盖区中的 c-Fos 表达。S32006 在 1-10mg/kg 剂量下诱导了纹状体和 NAcc 中内侧部分的 c-Fos 表达的相似增加，而它在 STN 和 SNr 的内侧部分中呈剂量依赖性地增强了 c-Fos 表达。这些药物均未在苍白球中诱导 c-Fos 表达。5-HT（2C）拮抗剂和反向激动剂引起的 c-Fos 表达的独特模式表明，在基底神经节对抑制 5-HT（2C）受体的药物的反应中存在细胞和功能异质性。
