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多巴胺受体的阻断可逆转内源性脑啡肽在尾状核而非伏隔核中的行为效应:δ和μ阿片受体的不同参与情况。

Blockade of dopamine receptors reverses the behavioral effects of endogenous enkephalins in the Nucleus caudatus but not in the Nucleus accumbens: differential involvement of delta and mu opioid receptors.

作者信息

Daugé V, Rossignol P, Roques B P

机构信息

Laboratoire de Pharmacologie, UER des Sciences Pharmaceutiques et Biologiques, Paris, France.

出版信息

Psychopharmacology (Berl). 1989;99(2):168-75. doi: 10.1007/BF00442803.

Abstract

We have previously (Daugé et al. 1988) demonstrated that injection of the mu agonist [D-Ala2, MePhe4, Gly-ol5]-enkephalin (DAGO) or the delta agonist [D-Thr2, Leu5]-enkephalyl-Thr6 (DTLET) into the rat Nucleus accumbens (N.Acc.), or Nucleus caudatus (N.Caud.) induced a hypoactivity followed by hyperactivity 150 min later in the case of the mu agonist and a hyperactivity in the case of the delta agonist. Moreover, naloxone reversible delta-type responses were obtained by local infusion of kelatorphan, ([(R)-3(N-hydroxylcarboxamido-2-benzylpropanoyl)-L-alanine]), a complete inhibitor of enkephalin catabolism, suggesting a tonic control of the behavioral activity of rat by the endogenous opioid peptides. In this work, the putative involvement of the dopaminergic system in these behavioral responses was investigated by using the DA antagonist thioproperazine. In the N.Acc., the behavioral effects of kelatorphan or of mu or delta agonists were not altered by thioproperazine-induced blockade of dopamine receptors. In contrast, the hyperactivity produced by DTLET or by kelatorphan in the N.Caud. was reversed by thioproperazine while the time-dependent biphasic effect resulting from DAGO injection remained unaffected by the DA antagonist. This blocking effect of thioproperazine is in agreement with the previously described delta-selective enhancement of the release of newly synthesized DA in the striatum but not in the N.Acc.

摘要

我们之前(Daugé等人,1988年)已证明,向大鼠伏隔核(N.Acc.)或尾状核(N.Caud.)注射μ激动剂[D-Ala2,MePhe4,Gly-ol5]-脑啡肽(DAGO)或δ激动剂[D-Thr2,Leu5]-脑啡肽-Thr6(DTLET),对于μ激动剂而言,会先引起活动减少,150分钟后出现活动亢进;对于δ激动剂,则会引起活动亢进。此外,通过局部注入凯拉托芬([(R)-3(N-羟基羧酰胺基-2-苄基丙酰基)-L-丙氨酸])(一种脑啡肽分解代谢的完全抑制剂)可获得纳洛酮可逆的δ型反应,这表明内源性阿片肽对大鼠的行为活动具有紧张性控制作用。在本研究中,通过使用多巴胺拮抗剂硫丙嗪来研究多巴胺能系统在这些行为反应中的可能作用。在伏隔核中,硫丙嗪诱导的多巴胺受体阻断并未改变凯拉托芬或μ或δ激动剂的行为效应。相反,硫丙嗪可逆转DTLET或凯拉托芬在尾状核中产生的活动亢进,而DAGO注射所导致的时间依赖性双相效应不受多巴胺拮抗剂的影响。硫丙嗪的这种阻断作用与先前描述的δ选择性增强纹状体中而非伏隔核中新合成多巴胺释放的现象一致。

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