Cervo L, Grignaschi G, Nowakowska E, Samanin R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Eur J Pharmacol. 1989 Nov 14;171(1):119-25. doi: 10.1016/0014-2999(89)90435-4.
1-(3-Trifluoromethylphenyl)piperazine (TFMPP), a serotonin1 (5-HT1) receptor agonist, injected i.p. in doses of 0.1 and 0.6 mg/kg, did not modify the immobility time of rats in the forced swimming test but significantly antagonized the effect of a 7 days treatment with 10 mg/kg per day desipramine (DMI). A similar effect was found on infusing 1 and 5 micrograms/microliters TFMPP bilaterally into the ventral tegmental area (VTA). Infusion of 5 micrograms/microliters TFMPP into the nucleus accumbens or into the globus pallidus did not modify the effect of DMI. The effect of 5 micrograms TFMPP infused into the VTA was prevented by the i.p. administration of 5 mg/kg metergoline, a non-selective serotonin receptor antagonist. Infusion of 5 micrograms/microliters 8-hydroxy-2-(di-n-propylamino)tetralin, a specific 5-HT1A receptor agonist, into the VTA did not modify the effect of DMI. Besides acting as a 5-HT1B receptor agonist, TFMPP may also act on other 5-HT receptor types, but available evidence suggests that its former action is more important. It thus appears that 5-HT1 receptors in the VTA, presumably of the 5-HT1B type, act by preventing the anti-immobility effect of DMI. The role of VTA dopamine and non-dopamine cells in the effect of TFMPP is discussed.
1-(3-三氟甲基苯基)哌嗪(TFMPP),一种5-羟色胺1(5-HT1)受体激动剂,腹腔注射剂量为0.1和0.6毫克/千克时,在强迫游泳试验中并未改变大鼠的不动时间,但显著拮抗了每天10毫克/千克地昔帕明(DMI)7天治疗的效果。在双侧腹侧被盖区(VTA)注入1和5微克/微升TFMPP时也发现了类似的效果。向伏隔核或苍白球注入5微克/微升TFMPP并未改变DMI的效果。腹腔注射5毫克/千克麦角林(一种非选择性5-羟色胺受体拮抗剂)可阻止注入VTA的5微克TFMPP的效果。向VTA注入5微克/微升8-羟基-2-(二正丙基氨基)四氢萘(一种特异性5-HT1A受体激动剂)并未改变DMI的效果。除了作为5-HT1B受体激动剂起作用外,TFMPP可能还作用于其他5-羟色胺受体类型,但现有证据表明其前一种作用更为重要。因此,VTA中的5-HT1受体,可能是5-HT1B型,似乎是通过阻止DMI的抗不动效果起作用的。文中讨论了VTA多巴胺能和非多巴胺能细胞在TFMPP作用中的作用。