Herndon J L, Pierson M E, Glennon R A
Department of Medical Chemistry, School of Pharmacy, Medical College of Virginia, Virginia Commonwealth University, Richmond 23298.
Pharmacol Biochem Behav. 1992 Nov;43(3):739-48. doi: 10.1016/0091-3057(92)90403-3.
Using a standard two-lever operant procedure with rats trained to discriminate 1-(3-trifluoromethylphenyl)piperazine (TFMPP) (0.5 mg/kg) from saline, tests of stimulus antagonism and stimulus generalization were performed to better understand the stimulus properties of this agent. The agents examined for ability to antagonize the TFMPP stimulus were prazosin, quipazine, zacopride, buspirone, 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT), 1-(2-methoxyphenol)-4-[4-(2-phthalimido)butyl]-piperazine (NAN-190), haloperidol, and 1-(2-pyrimidinyl)piperazine (1-PP); only buspirone attenuated the response to TF-MPP. In separate experiments, the lowest nondisrupting dose of buspirone (1.2 mg/kg) caused a rightward shift of the TFMPP dose-response curve (TFMPP alone, ED50 = 0.19 mg/kg; TFMPP + buspirone, ED50 = 0.43 mg/kg). In addition, 3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo[3,2-b]pyrid-5-one (CP 93, 129), 7-trifluoromethyl-4-(4-methyl-1-piperazinyl)pyrolo[1,2-a]quinox ali ne (CGS 12066B), 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), 3-chlorophenylbiguanide (mCPBG), NAN-190, nisoxetine, zacopride, 1-PP, (+)-N-allylnormetazocine ((+)-NANM), and N-methyl-1-(3,4-methylenedioxyphenyl)-2-aminopropane (MDMA) were analyzed in tests of stimulus generalization. The TFMPP stimulus generalized only to CGS 12066B (ED50 = 4.2 mg/kg) and (+)-NANM (ED50 = 8.8 mg/kg). Tests with DOI and MDMA resulted in partial generalization. Up to doses that disrupted behavior, all other agents had little effect on TFMPP-appropriate responding. The results of these and other published studies suggest roles for 5-hydroxytryptamine 1B (5-HT1B), 5-HT1C, and, possibly, sigma-receptors in the mediation of the TFMPP stimulus and indicate a lack of involvement of 5-HT1A, 5-HT2, dopaminergic, and adrenergic mechanisms in this behavior.
采用标准的双杠杆操作性条件反射程序，训练大鼠区分1-（3-三氟甲基苯基）哌嗪（TFMPP，0.5毫克/千克）和生理盐水，进行刺激拮抗和刺激泛化测试，以更好地了解该药物的刺激特性。检测了哌唑嗪、喹哌嗪、扎考必利、丁螺环酮、8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）、1-（2-甲氧基苯酚）-4-[4-（2-邻苯二甲酰亚胺基）丁基]-哌嗪（NAN-190）、氟哌啶醇和1-（2-嘧啶基）哌嗪（1-PP）拮抗TFMPP刺激的能力；只有丁螺环酮减弱了对TF-MPP的反应。在单独的实验中，丁螺环酮的最低无干扰剂量（1.2毫克/千克）使TFMPP剂量-反应曲线右移（单独使用TFMPP时，ED50 = 0.19毫克/千克；TFMPP + 丁螺环酮时，ED50 = 0.43毫克/千克）。此外，在刺激泛化测试中分析了3-（1,2,5,6-四氢吡啶-4-基）吡咯并[3,2-b]吡啶-5-酮（CP 93,129）、7-三氟甲基-4-（4-甲基-1-哌嗪基）吡咯并[1,2-a]喹喔啉（CGS 12066B）、1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI）、3-氯苯基双胍（mCPBG）、NAN-190、尼索西汀、扎考必利、1-PP、（+）-N-烯丙基去甲美沙酮（（+）-NANM）和N-甲基-1-（3,4-亚甲二氧基苯基）-2-氨基丙烷（MDMA）。TFMPP刺激仅泛化到CGS 12066B（ED50 = 4.2毫克/千克）和（+）-NANM（ED50 = 8.8毫克/千克）。DOI和MDMA的测试导致部分泛化。在达到破坏行为的剂量之前，所有其他药物对TFMPP相关反应几乎没有影响。这些研究以及其他已发表研究的结果表明，5-羟色胺1B（5-HT1B）、5-HT1C以及可能的σ受体在TFMPP刺激的介导中起作用，并表明5-HT1A、5-HT2、多巴胺能和肾上腺素能机制不参与此行为。
