Influence of glucocorticoids on dopaminergic transmission in the rat dorsolateral striatum

Influence of glucocorticoids on dopaminergic transmission in the rat dorsolateral striatum
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DOI:
10.1046/j.1460-9568.2001.01434.x
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发表时间:
2001-02-01
影响因子:
3.4
通讯作者:
Piazza, PV
Piazza, PV
中科院分区:
医学3区
文献类型:
--
作者:
Barrot, M;Abrous, DN;Piazza, PV

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糖皮质激素对中枢神经递质系统有很强的影响。在目前的工作中,我们研究的功能后果皮质酮抑制多巴胺能传递的背外侧纹状体通过研究Fos样蛋白的表达和细胞外多巴胺水平。肾上腺切除术抑制了糖皮质激素,恢复生理血浆皮质酮浓度的影响的特异性进行评估。我们发现,在背外侧纹状体,糖皮质激素修改突触后多巴胺能传递。抑制糖皮质激素可降低多巴胺D-1受体直接激动剂(SKF 82958,1.5 mg/kg,i. p.)对Fos蛋白的诱导,但对吗啡(2 mg/kg,s.c.)或多巴胺合成的限制酶酪氨酸羟化酶的密度。与对吗啡的多巴胺能反应相反,对可卡因(15 mg/kg,i. p.)被皮质酮的抑制所改变在这种情况下,肾上腺切除术增加可卡因诱导的细胞外多巴胺的变化,但没有修改Fos样蛋白的表达。可卡因诱导的Fos样蛋白的变化可能是由于多巴胺能反应的增加和多巴胺D-1受体功能活性的降低之间的补偿机制。对可卡因的增加的多巴胺能反应也与先前在丘脑核壳中观察到的降低的反应形成对比[Barrot等人(2000)Eur.神经科学杂志,12,973-979]。目前的数据突出了糖皮质激素在多巴胺能投射中的深刻异质性影响。
Glucocorticoid hormones exert strong influences on central neurotransmitter systems. In the present work, we examined the functional consequences of corticosterone suppression on the dopaminergic transmission in the dorsolateral striatum by studying the expression of Fos-like proteins and extracellular dopamine levels. Glucocorticoid hormones were suppressed by adrenalectomy, and the specificity of the effects assessed by restoring physiological plasmatic corticosterone concentrations. We show that, in the dorsolateral striatum, glucocorticoids modify postsynaptic dopaminergic transmission. Suppression of glucocorticoids decreased the induction of Fos proteins in response to a direct agonist of dopamine D-1 receptors (SKF 82958, 1.5 mg/kg, i.p.), but not the release of dopamine induced by morphine (2 mg/kg, s.c.) or the density of the limiting enzyme of dopamine synthesis, tyrosine hydroxylase. In contrast to the dopaminergic response to morphine, the response to cocaine (15 mg/kg, i.p.) was modified by the suppression of corticosterone. In this case, adrenalectomy increased cocaine-induced changes in extracellular dopamine but did not modify the expression of Fos-like proteins. This absence of changes in cocaine-induced Fos-like proteins might result from a compensatory mechanism between the increase in the dopaminergic response and the decrease in the functional activity of dopamine D-1 receptors. The increased dopaminergic response to cocaine also contrasts with the decreased response previously observed in the shell of the nucleus accumbens [Barrot et al. (2000) Eur. J. Neurosci., 12, 973-979]. The present data highlight the profound heterogeneous influence of glucocorticoids within dopaminergic projections.