Cervo L, Samanin R
Istituto di Ricerche Farmacologiche Mario Negri, Milan, Italy.
Psychopharmacology (Berl). 1991;103(4):524-8. doi: 10.1007/BF02244253.
The effect of chronic treatment with 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT) on rats' behaviour in the forced swimming test was studied in animals injected intracerebroventricularly with 150 micrograms 5,7-dihydroxytryptamine (5,7-DHT) or given three oral doses of parachlorophenylalanine (PCPA). A single dose of 0.25 mg/kg 8-OH-DPAT significantly reduced rats' immobility in 5,7-DHT-sham-operated animals 24 h after a 14-day schedule of 0.25 mg/kg 8-OH-DPAT or saline subcutaneously twice daily. The effects of acute 8-OH-DPAT in both chronically 8-OH-DPAT- and saline-treated animals were prevented by 5,7-DHT which caused a marked depletion of brain serotonin (5-HT). Since animals treated with both 8-OH-DPAT and 5,7-DHT were more active in an open field than those receiving the substances separately, the forced swimming behaviour was analyzed in more detail in subsequent experiments. PCPA treatment completely prevented the increase in struggling caused by acute and chronic 8-OH-DPAT, administered as in the previous experiment, but did not modify the reduction of floating caused by 8-OH-DPAT. PCPA and 8-OH-DPAT, alone or in combination, did not modify rats' activity in an open field. Finally, 0.5 and 1.0 micrograms 8-OH-DPAT in the nucleus raphe dorsalis significantly increased struggling and reduced floating to the same extent in animals which had received 0.25 mg/kg 8-OH-DPAT or saline subcutaneously twice daily for 14 days. It thus appears that the antidepressant-like effects of chronic treatment with 8-OH-DPAT in the forced swimming test require the integrity of presynaptic serotonergic mechanisms.
在脑室内注射150微克5,7 - 二羟基色胺（5,7 - DHT）或口服三次对氯苯丙氨酸（PCPA）的动物中，研究了用8 - 羟基 - 2 - （二正丙基氨基）四氢萘（8 - OH - DPAT）进行慢性治疗对大鼠强迫游泳试验行为的影响。在以0.25毫克/千克8 - OH - DPAT或生理盐水每日两次皮下注射14天的方案后，单剂量0.25毫克/千克8 - OH - DPAT显著降低了5,7 - DHT假手术动物24小时后的不动时间。5,7 - DHT导致脑血清素（5 - HT）显著耗竭，从而阻止了急性8 - OH - DPAT对长期接受8 - OH - DPAT和生理盐水治疗动物的影响。由于同时接受8 - OH - DPAT和5,7 - DHT治疗的动物在旷场中比单独接受这些物质的动物更活跃，因此在后续实验中对强迫游泳行为进行了更详细的分析。如前一实验那样给予PCPA治疗完全阻止了急性和慢性8 - OH - DPAT引起的挣扎增加，但并未改变8 - OH - DPAT引起的漂浮减少。单独或联合使用PCPA和8 - OH - DPAT均未改变大鼠在旷场中的活动。最后，在中缝背核注射0.5微克和1.0微克8 - OH - DPAT在接受0.25毫克/千克8 - OH - DPAT或生理盐水每日两次皮下注射14天的动物中，显著增加了挣扎并同等程度地减少了漂浮。因此，在强迫游泳试验中，8 - OH - DPAT慢性治疗的抗抑郁样作用似乎需要突触前5 - HT能机制的完整性。
