Laboratories of Pharmacology Toxicology, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Br J Pharmacol. 2012 May;166(2):788-800. doi: 10.1111/j.1476-5381.2011.01815.x.
Dopamine released from the endings of descending dopaminergic nerve fibres in the spinal cord may be involved in modulating functions such as locomotion and nociception. Here, we examined the effects of dopamine on spinal synaptic transmissions in rats.
Spinal reflex potentials, monosynaptic reflex potential (MSR) and slow ventral root potential (sVRP), were measured in the isolated spinal cord of the neonatal rat. Dopamine release was measured by HPLC.
Dopamine at lower concentrations (<1 µM) depressed sVRP, which is a C fibre-evoked polysynaptic response and believed to reflect nociceptive transmission. At higher concentrations (>1 µM), in addition to a potent sVRP depression, dopamine depolarized baseline potential and slightly depressed MSR. Depression of sVRP by dopamine was partially reversed by dopamine D(1) -like but not by D(2) -like receptor antagonists. SKF83959 and SKF81297, D(1) -like receptor agonists, and methamphetamine, an endogenous dopamine releaser, also caused the inhibition of sVRP. Methamphetamine also depressed MSR, which was inhibited by ketanserin, a 5-HT(2A/2C) receptor antagonist. Methamphetamine induced the release of dopamine and 5-HT from spinal cords, indicating that the release of endogenous dopamine and 5-HT depresses sVRP and MSR respectively.
These results suggested that dopamine at lower concentrations preferentially inhibited sVRP, which is mediated via dopamine D(1) -like and other unidentified receptors. The dopamine-evoked depression is involved in modulating the spinal functions by the descending dopaminergic pathways.
脊髓下行多巴胺能神经末梢释放的多巴胺可能参与调节运动和痛觉等功能。本研究旨在观察多巴胺对大鼠脊髓突触传递的影响。
在新生大鼠离体脊髓中测量脊髓反射电位、单突触反射电位（MSR）和慢腹根电位（sVRP）。通过 HPLC 测量多巴胺的释放。
较低浓度（<1 μM）的多巴胺可抑制 sVRP，这是一种 C 纤维诱发的多突触反应，被认为反映了痛觉传递。较高浓度（>1 μM）时，除了强烈抑制 sVRP 外，多巴胺还使基线电位去极化，并轻微抑制 MSR。多巴胺 D1 样而非 D2 样受体拮抗剂可部分逆转多巴胺对 sVRP 的抑制作用。D1 样受体激动剂 SKF83959 和 SKF81297 以及内源性多巴胺释放剂苯丙胺也可抑制 sVRP。苯丙胺还可抑制 MSR，5-HT2A/2C 受体拮抗剂酮色林可抑制 MSR。苯丙胺可诱发脊髓中多巴胺和 5-HT 的释放，表明内源性多巴胺和 5-HT 的释放分别抑制 sVRP 和 MSR。
这些结果表明，较低浓度的多巴胺优先抑制 sVRP，这是通过多巴胺 D1 样和其他未鉴定的受体介导的。下行多巴胺能通路诱发的抑制作用可能参与调节脊髓功能。
