Tung C S, Grenhoff J, Svensson T H
Department of Pharmacology, Karolinska Institute, Stockholm, Sweden.
J Neural Transm Gen Sect. 1991;84(1-2):53-64. doi: 10.1007/BF01249109.
The acute effect of systemic administration of the antipsychotic drug haloperidol on the activity of midbrain dopamine (DA) neurons was investigated with extracellular single cell recording in the chloral hydrate anaesthetized male rat. DA cells in the zona compacta-substantia nigra (SN) and ventral tegmental area (VTA) were excited by low doses of haloperidol. This excitation, which included increased firing rate and burst firing, was no longer present after treatment with the excitatory amino acid (EAA) antagonist kynurenate (1 mumol ICV). Kynurenate alone profoundly regularized the activity and abolished burst firing in VTA-DA neurons, while SN-DA neuronal activity was unaffected by this treatment. Thus, VTA-DA neurons, but not SN neurons, appear to be dependent on a tonic EAA input for their normal varied, burst-firing activity. The antagonism of haloperidol-induced effects by kynurenate suggests that the acute excitatory action of haloperidol on midbrain DA neurons is executed via EAA neurons, in the case of the VTA probably via a corticofugal EAA pathway from the medial prefrontal cortex.
采用细胞外单细胞记录技术，在水合氯醛麻醉的雄性大鼠中，研究了全身给予抗精神病药物氟哌啶醇对中脑多巴胺（DA）能神经元活动的急性影响。低剂量的氟哌啶醇可兴奋致密部-黑质（SN）和腹侧被盖区（VTA）中的DA能细胞。这种兴奋作用，包括放电频率增加和爆发式放电，在用兴奋性氨基酸（EAA）拮抗剂犬尿烯酸（1 μmol，脑室内注射）处理后不再出现。单独使用犬尿烯酸可显著调节VTA-DA能神经元的活动并消除爆发式放电，而SN-DA能神经元的活动不受此处理的影响。因此，VTA-DA能神经元而非SN神经元，其正常的多样爆发式放电活动似乎依赖于持续性的EAA输入。犬尿烯酸对氟哌啶醇诱导效应的拮抗作用表明，氟哌啶醇对中脑DA能神经元的急性兴奋作用是通过EAA能神经元介导的，就VTA而言，可能是通过来自内侧前额叶皮质的皮质-离中EAA通路。
