Edwards E, Harkins K, Wright G, Henn F
Department of Psychiatry and Behavioral Science, State University of New York, Stony Brook 11794-8101.
J Neurochem. 1991 May;56(5):1581-6. doi: 10.1111/j.1471-4159.1991.tb02054.x.
The effects of learned helplessness on the 5-hydroxytryptamine (5-HT) uptake site were studied in rats using [3H]paroxetine binding. This ligand was chosen because it was demonstrated to label directly the 5-HT uptake site whereas the [3H]imipramine binding site has been demonstrated to be heterogeneous in nature. Moreover, [3H]imipramine appears to bind to a presynaptic recognition site different from the uptake site. Exposure to uncontrollable shock training and testing resulted in an overall increase in [3H]paroxetine binding in all the groups studied [nonhelpless (NLH), learned helpless (LH), spontaneously helpless (SPLH)] as compared to naive controls (NC). However, the increase in [3H]paroxetine binding was significantly higher in the LH and SPLH groups. The maximum number of [3H]paroxetine binding sites in the rat hippocampus was increased significantly in learned helpless rats (LH and SPLH) at day 4 and day 30 after the shock escape test as compared to NC and NLH rats. By contrast, in the rat hypothalamus the maximum number of [3H]paroxetine binding sites was reduced significantly in the LH rats as compared to naive controls and NLH rats during the same time course. There was no change in [3H]paroxetine binding sites in any other brain regions examined in LH, NLH, and NC rats. The results suggest that a hippocampal hypothalamic connection might play a role in the serotonergic mediation of learned helpless behavior.
利用[3H]帕罗西汀结合法，在大鼠中研究了习得性无助对5-羟色胺（5-HT）摄取位点的影响。选择这种配体是因为它被证明可直接标记5-HT摄取位点，而[3H]丙咪嗪结合位点本质上已被证明是异质性的。此外，[3H]丙咪嗪似乎与不同于摄取位点的突触前识别位点结合。与未经历过的对照大鼠（NC）相比，接受不可控电击训练和测试导致所有研究组[非无助（NLH）、习得性无助（LH）、自发无助（SPLH）]中[3H]帕罗西汀结合总体增加。然而，LH组和SPLH组中[3H]帕罗西汀结合的增加显著更高。与NC组和NLH组大鼠相比，在电击逃避测试后第4天和第30天，习得性无助大鼠（LH组和SPLH组）海马中[3H]帕罗西汀结合位点的最大数量显著增加。相比之下，在相同时间进程中，与未经历过的对照大鼠和NLH组大鼠相比，LH组大鼠下丘脑[3H]帕罗西汀结合位点的最大数量显著减少。在LH组、NLH组和NC组大鼠中，其他任何检查的脑区中[3H]帕罗西汀结合位点均无变化。结果表明，海马-下丘脑连接可能在习得性无助行为的5-羟色胺能介导中起作用。
