腹侧被盖区中D1受体激动剂增强D2受体激动剂诱导的抑制作用。

Enhancement of D2 receptor agonist-induced inhibition by D1 receptor agonist in the ventral tegmental area.

Momiyama T, Sasa M, Takaori S

Department of Pharmacology, Faculty of Medicine, Kyoto University, Japan.

Br J Pharmacol. 1993 Oct;110(2):713-8. doi: 10.1111/j.1476-5381.1993.tb13870.x.

Abstract

A microiontophoretic study was performed on chloral hydrate-anaesthetized rats to examine the role of D1 receptors in the ventral tegmental area (VTA) neurones, which are inhibited by autoreceptor and D2 receptor agonists. 2. Inhibition by microiontophoretic application of quinpirole (a D2 agonist) of antidromic spikes elicited by stimulation of the nucleus accumbens in dopaminergic neurones of the VTA, was significantly enhanced by simultaneous application of SKF 38393 (D1 agonist), although SKF 38393 alone had little effect on the neurones. 3. In addition, quinpirole-induced inhibition was antagonized by iontophoretic application of domperidone (D2 antagonist), but was not affected by SCH 23390 (D1 antagonist). 4. Furthermore, SKF 38393-induced enhancement of inhibition by quinpirole was antagonized by simultaneous application of SCH 23390. 5. These results suggest that activation of D1 receptors located on the VTA dopaminergic neurones or on non-dopaminergic nerve terminals is not essential for inducing inhibition of the dopaminergic neurones, but enhances D2 receptor-mediated inhibition directly or indirectly via inhibitory neurones.

摘要

对水合氯醛麻醉的大鼠进行了微离子透入研究，以检验D1受体在腹侧被盖区（VTA）神经元中的作用，这些神经元会被自身受体和D2受体激动剂抑制。2. 在VTA多巴胺能神经元中，通过微离子透入法施加喹吡罗（一种D2激动剂）对伏隔核刺激引发的逆向动作电位的抑制作用，在同时施加SKF 38393（D1激动剂）时显著增强，尽管单独使用SKF 38393对神经元几乎没有影响。3. 此外，喹吡罗诱导的抑制作用可被离子透入法施加多潘立酮（D2拮抗剂）拮抗，但不受SCH 2339（D1拮抗剂）影响。4. 此外，同时施加SCH 23390可拮抗SKF 38393诱导的喹吡罗抑制增强作用。5. 这些结果表明，位于VTA多巴胺能神经元或非多巴胺能神经末梢上的D1受体的激活对于诱导多巴胺能神经元的抑制并非必不可少，但可直接或通过抑制性神经元间接增强D2受体介导的抑制作用。