Kitamura Y, Nagatani T
Laboratory for Pharmacology, Asahi Chemical Industry Co., Ltd., Shizuoka, Japan.
Pharmacol Biochem Behav. 1996 Nov;55(3):445-51. doi: 10.1016/s0091-3057(96)00116-5.
We studied the effects of buspirone and 8-hydroxy-2-(di-n-propylamino) tetralin (8-OH-DPAT) on duration of immobility in mice in the forced swim test. Buspirone [3-10 mg/kg, intraperitoneally (IP)] potently and dose dependently increased the duration of immobility in mice. In contrast, following a single dose of 8-OH-DPAT (1-3 mg/kg, IP), there was a dose-dependent decrease in the duration of immobility. Pretreatment with the 5-HT synthesis inhibitor p-chlorophenylalanine (200 mg/kg, IP, 3 days before further drug treatment) did not alter the effects of buspirone or 8-OH-DPAT. The increase in the duration of immobility induced by buspirone (3 mg/kg, IP) was blocked by NAN-190 [1-(2-methoxyphenyl)-4-(4-[2-phthalimido]butyl)-piperazine hydrobromide, 1 mg/kg, IP], a postsynaptic 5-HT1A receptor antagonist. However, the effect of 8-OH-DPAT (1 mg/kg, IP) was not blocked by NAN-190 (1 mg/kg, IP). The effect of buspirone (3 mg/kg, IP) was blocked by apomorphine (0.3 mg/kg, IP), a dopamine receptor agonist. Based on the results of this study, it is suggested that the effects of buspirone and of 8-OH-DPAT on immobility in the forced swim test may occur through different mechanisms.
我们在强迫游泳试验中研究了丁螺环酮和8-羟基-2-(二正丙基氨基)四氢萘(8-OH-DPAT)对小鼠不动时间的影响。丁螺环酮[3-10毫克/千克，腹腔注射(IP)]能有效且剂量依赖性地增加小鼠的不动时间。相比之下，单次注射8-OH-DPAT(1-3毫克/千克，IP)后，不动时间呈剂量依赖性减少。用5-羟色胺合成抑制剂对氯苯丙氨酸(200毫克/千克，IP，在进一步药物治疗前3天)预处理并没有改变丁螺环酮或8-OH-DPAT的作用。丁螺环酮(3毫克/千克，IP)诱导的不动时间增加被突触后5-HT1A受体拮抗剂NAN-190[1-(2-甲氧基苯基)-4-(4-[2-邻苯二甲酰亚胺基]丁基)-哌嗪氢溴酸盐，1毫克/千克，IP]阻断。然而，8-OH-DPAT(1毫克/千克，IP)的作用未被NAN-190(1毫克/千克，IP)阻断。丁螺环酮(3毫克/千克，IP)的作用被多巴胺受体激动剂阿扑吗啡(0.3毫克/千克，IP)阻断。基于本研究结果，提示丁螺环酮和8-OH-DPAT在强迫游泳试验中对不动的影响可能通过不同机制发生。
