Bervoets K, Millan M J, Colpaert F C
FONDAX, Neurobiology Division, Puteaux, France.
Eur J Pharmacol. 1990 Nov 27;191(2):185-95. doi: 10.1016/0014-2999(90)94146-o.
In rats lightly restrained in plastic cylinders, subcutaneous administration of the selective, high efficacy 5-HT1A receptor agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), induced spontaneous tail-flicks, that is, tail-flicks in the absence of extraneous stimulation. The putative 5-HT1B receptor agonist, CGS 12066B, the mixed 5-HT1B/1C receptor agonists, 1-((3-(trifluoromethyl)phenyl]piperazine (TFMPP) and 1-(3-chlorophenyl)piperazine (mCPP), the 5-HT1C/2 receptor agonist, [+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and the 5-HT1B/1C/2 receptor agonist, quipazine, did not, in contrast, elicit tail-flicks when applied alone. However, TFMPP, mCPP, DOI and quipazine, but not CGS 12066B, each potentiated the action of 8-OH-DPAT. Further, in the presence of TFMPP, mCPP and DOI, the dose-response curve for the induction of tail-flicks by 8-OH-DPAT was both steeper and shifted to the left. Tail-flicks induced by another high efficacy 5-HT1A receptor agonist, lisuride, were also enhanced by TFMPP, mCPP and DOI. The 5-HT1A receptor partial agonists, buspirone and (+/-)-flesinoxan, evoked tail-flicks only in the presence of TFMPP, mCPP or DOI. The mixed 5-HT1C/2 receptor antagonists, ritanserin and ICI 169,369, did not modify the action of 8-OH-DPAT alone but abolished the potentiation of 8-OH-DPAT-induced tail-flicks by DOI and TFMPP. Further, the selective 5-HT1A receptor antagonist, BMY 7378, blocked tail-flicks induced by both 8-OH-DPAT alone and 8-OH-DPAT plus DOI or TFMPP. A common property of those drugs potentiating 8-OH-DPAT-induced tail-flicks is an agonist action at 5-HT1C receptors and the data indicate that it is this mechanism which underlies the facilitation of tail-flicks.
在轻度束缚于塑料圆筒中的大鼠身上，皮下注射选择性、高效的5-羟色胺1A（5-HT1A）受体激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）会诱发自发甩尾，即在无外界刺激情况下的甩尾。相比之下，假定的5-HT1B受体激动剂CGS 12066B、5-HT1B/1C混合型受体激动剂1-（3-三氟甲基苯基）哌嗪（TFMPP）和1-（3-氯苯基）哌嗪（mCPP）、5-HT1C/2受体激动剂（±）-1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）以及5-HT1B/1C/2受体激动剂喹哌嗪单独应用时均未引发甩尾。然而，TFMPP、mCPP、DOI和喹哌嗪（但不是CGS 12066B）均增强了8-OH-DPAT的作用。此外，在存在TFMPP、mCPP和DOI的情况下，8-OH-DPAT诱发甩尾的剂量-反应曲线更陡峭且向左移动。另一种高效5-HT1A受体激动剂利舒脲诱发的甩尾也被TFMPP、mCPP和DOI增强。5-HT1A受体部分激动剂丁螺环酮和（±）-氟辛克生仅在存在TFMPP、mCPP或DOI时才诱发甩尾。5-HT1C/2混合型受体拮抗剂利坦色林和ICI 169,369单独应用时不改变8-OH-DPAT的作用，但消除了DOI和TFMPP对8-OH-DPAT诱发甩尾的增强作用。此外，选择性5-HT1A受体拮抗剂BMY 7378阻断了8-OH-DPAT单独诱发的甩尾以及8-OH-DPAT加DOI或TFMPP诱发的甩尾。那些增强8-OH-DPAT诱发甩尾作用的药物的一个共同特性是对5-HT1C受体具有激动作用, 数据表明正是这一机制构成了甩尾促进作用的基础。
