Filip M, Przegaliński E
Institute of Pharmacology, Polish Academy of Sciences, Kraków, Poland.
Pol J Pharmacol. 1996 Jul-Aug;48(4):397-402.
To examine the effects of 4-[3-(benzotriazol-1-yl)-propyl]-1-(2-methoxyphenyl)piperazine (MP-3022), a high affinity 5-HT1A ligand, on the 5-HT1A-induced stimulus effect and to compare its effects with those produced by some 5-HT1A receptor ligands, rats were trained to discriminate between 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), 0.1 mg/kg ip, and saline in a standard, two-lever operant procedure. Substitution studies showed that the 8-OH-DPAT cue was mimicked in a dose-dependent manner by buspirone and ipsapirone, the 5-HT1A receptor partial agonists, but not by 1-(3-chlorophenyl)piperazine (m-CPP), a nonselective 5-HT agonist. Furthermore, the 8-OH-DPAT cue was almost completely blocked by 1-(2-methoxyphenyl)-4-[4-(2-phthalimido)]butylpiperazine (NAN-190), a 5-HT1A receptor and alpha 1-adrenoceptor antagonist, but not by prazosin (a selective alpha 1-adrenoceptor blocker). Our results also demonstrate that the discriminative effect of 8-OH-DPAT may be dose-dependently antagonized by MP-3022, which itself does not mimic the cue. It is concluded that MP-3022 behaves like a full 5-HT1A receptor antagonist in the 8-OH-DPAT-evoked discrimination procedure.
为研究高亲和力5-HT1A配体4-[3-(苯并三唑-1-基)-丙基]-1-(2-甲氧基苯基)哌嗪(MP-3022)对5-HT1A诱导的刺激效应的影响，并将其效应与某些5-HT1A受体配体产生的效应进行比较，采用标准的双杠杆操作性程序，训练大鼠区分腹腔注射0.1mg/kg的8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)和生理盐水。替代研究表明，5-HT1A受体部分激动剂丁螺环酮和伊沙匹隆能以剂量依赖的方式模拟8-OH-DPAT提示，但非选择性5-HT激动剂1-(3-氯苯基)哌嗪(m-CPP)则不能。此外，5-HT1A受体和α1-肾上腺素能受体拮抗剂1-(2-甲氧基苯基)-4-[4-(2-邻苯二甲酰亚胺)]丁基哌嗪(NAN-190)几乎能完全阻断8-OH-DPAT提示，但哌唑嗪(一种选择性α1-肾上腺素能受体阻滞剂)则不能。我们的结果还表明，MP-3022可剂量依赖性地拮抗8-OH-DPAT的辨别效应，而其本身并不模拟该提示。结论是，在8-OH-DPAT诱发的辨别程序中，MP-3022表现得像一种完全的5-HT1A受体拮抗剂。
