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[终纹床核的γ-氨基丁酸能和多巴胺能机制参与经由下丘脑外侧介导的精神药物强化作用]

[Participation of GABA- and dopaminergic mechanisms of the bed nucleus of stria terminalis in reinforcing effects of psychotropic drugs mediated via the lateral hypothalamus].

作者信息

Shabanov P D, Lebedev A A

出版信息

Ross Fiziol Zh Im I M Sechenova. 2011 Aug;97(8):804-13.

Abstract

The purpose of the investigation was to elucidate significance of GABA and dopamine systems of the bed nucleus of stria terminalis for the reinforcing effects of a number of psychotropic drugs (opiates, opioids, psychostimulants) on self-stimulation of the lateral hypothalamus in rats. To the Wistar male rats, bipolar electrodes were implanted in the lateral hypothalamus to study self-stimulation reaction in the Skinner box. Simultaneously, the microcannules were implanted into the bed nucleus of stria terminalis to inject the drugs under study. Some drugs, xycaine, or lidocain, a blocker of sodium influx ionic currents, antagonists of GABAA receptors bicuculline, D1 dopamine receptors SCH23390 and D2 dopamine receptors sulpiride which were administered intrastructurally into the bed nucleus of stria terminalis, were used for pharmacological analysis. Xycaine > SCH23390 = bicuculline inhibited self-stimulation of the lateral hypothalamus. The reinforcing properties of a number of psychoactive drugs (amphetamine, Fentanyl, sodium ethaminal and leuenkephaline) were changed on the background of their action. It is concluded that the bed nucleus of stria terminalis controls the hypothalamic self-stimulation via GABA- and dopaminergic mechanisms. GABA realizes the negative (inhibitory) action. The direct positive (activating) effect on the lateral hypothalamus is realized through D1 dopamine receptors, and D2 dopamine receptors of the bed nucleus of stria terminalis limit the positive effects of narcogenic drugs.

摘要

本研究的目的是阐明终纹床核的γ-氨基丁酸(GABA)和多巴胺系统对多种精神药物(阿片类、阿片样物质、精神兴奋剂)增强大鼠下丘脑外侧区自我刺激作用的意义。对雄性Wistar大鼠,将双极电极植入下丘脑外侧区,以研究其在斯金纳箱中的自我刺激反应。同时,将微插管植入终纹床核,以便注射受试药物。使用了一些药物,如利多卡因(一种钠内流离子电流阻滞剂)、GABAA受体拮抗剂荷包牡丹碱、D1多巴胺受体拮抗剂SCH23390和D2多巴胺受体拮抗剂舒必利,将它们经结构内注射到终纹床核进行药理学分析。利多卡因>SCH23390 = 荷包牡丹碱抑制下丘脑外侧区的自我刺激。多种精神活性药物(苯丙胺、芬太尼、硫喷妥钠和亮氨酸脑啡肽)的强化特性在其作用背景下发生了改变。得出的结论是,终纹床核通过GABA能和多巴胺能机制控制下丘脑的自我刺激。GABA发挥负性(抑制性)作用。对下丘脑外侧区的直接正性(激活)作用通过D1多巴胺受体实现,而终纹床核的D2多巴胺受体限制了致幻药物的正性作用。

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