Maćkowiak Marzena, Grzegorzewska Małgorzata, Budziszewska Bogusława, Chocyk Agnieszka, Hess Grzegorz, Wedzony Krzysztof
Laboratory of Pharmacology and Brain Biostructure, Institute of Pharmacology, Polish Academy of Sciences, 12 Smetna Street, 31-343 Kraków, Poland.
Eur J Neurosci. 2008 Jun;27(11):2928-37. doi: 10.1111/j.1460-9568.2008.06255.x.
The present study investigated a potential role for glucocorticoid (GR) and mineralocorticoid (MR) receptors in the detrimental effects of single cocaine (COC) administration on both the number of polysialylated neural cell adhesion molecule (PSA-NCAM)-positive neurons and the induction of long-term potentiation (LTP) in the rat dentate gyrus (DG). The effects of COC (15 mg/kg i.p.) on the number of PSA-NCAM-positive neurons and the induction of LTP observed 2 days after COC administration were abolished either by depleting circulating corticosterone after administration of metyrapone (100 mg/kg s.c. given 3 h before COC) or by pharmacologically blocking GRs using mifepristone (RU 38486, 10 mg/kg s.c. given 1 h before COC). Administration of the MR blocker spironolactone (50 mg/kg s.c. given 1 h before COC) did not alter the effects of COC on the number of PSA-NCAM-positive neurons or LTP induction. Results have also shown that COC does not change the rate of cell proliferation, as measured by the presence of Ki-67 and the incorporation of bromodeoxyuridine (100 mg/kg i.p. given 2 h after COC) into the newly born cells in the DG 2 days after COC administration. Finally, we observed that GRs colocalized with some, but not all, PSA-NCAM-positive neurons, whereas MRs showed no colocalization with neurons positive for PSA-NCAM in the DG. These data indicate that a single dose of COC may arrest hippocampal susceptibility to plastic changes and lead to functional impairments through the alteration of hippocampal structure and the formation of memory traces.
本研究调查了糖皮质激素（GR）和盐皮质激素（MR）受体在单次给予可卡因（COC）对大鼠齿状回（DG）中多唾液酸神经细胞黏附分子（PSA-NCAM）阳性神经元数量及长时程增强（LTP）诱导的有害影响中所起的潜在作用。COC（15mg/kg腹腔注射）给药2天后观察到的对PSA-NCAM阳性神经元数量及LTP诱导的影响，在给予美替拉酮（在COC给药前3小时皮下注射100mg/kg）以耗尽循环皮质酮后，或在使用米非司酮（RU 38486，在COC给药前1小时皮下注射10mg/kg）药理学阻断GR后均被消除。在COC给药前1小时皮下注射MR阻断剂螺内酯（50mg/kg），并未改变COC对PSA-NCAM阳性神经元数量或LTP诱导的影响。结果还表明，COC并未改变细胞增殖速率，这通过Ki-67的存在及COC给药2天后DG中新生细胞中溴脱氧尿苷（腹腔注射100mg/kg，在COC给药后2小时给予）的掺入来衡量。最后，我们观察到GR与部分而非全部PSA-NCAM阳性神经元共定位，而在DG中MR与PSA-NCAM阳性神经元未显示共定位。这些数据表明，单次剂量的COC可能会抑制海马对可塑性变化的易感性，并通过改变海马结构和记忆痕迹的形成导致功能损害。
