Bracci Enrico, Centonze Diego, Bernardi Giorgio, Calabresi Paolo
Clinica Neurologica, Dipartimento di Neuroscienze, Università "Tor Vergata," Rome 00133, Italy.
J Neurophysiol. 2002 Apr;87(4):2190-4. doi: 10.1152/jn.00754.2001.
The striatum is the main recipient of dopaminergic innervation. Striatal projection neurons are controlled by cholinergic and GABAergic interneurons. The effects of dopamine on projection neurons and cholinergic interneurons have been described. Its action on GABAergic interneurons, however, is still unknown. We studied the effects of dopamine on fast-spiking (FS) GABAergic interneurons in vitro, with intracellular recordings. Bath application of dopamine elicited a depolarization accompanied by an increase in membrane input resistance (an effect that persisted in the presence of tetrodotoxin) and action-potential discharge. These effects were mimicked by the D1-like dopamine receptor agonist SKF38393 but not by the D2-like agonist quinpirole. Evoked corticostriatal glutamatergic synaptic currents were not affected by dopamine. Conversely, GABAergic currents evoked by intrastriatal stimulation were reversibly depressed by dopamine and D2-like, but not D1-like, agonists. Cocaine elicited effects similar to those of dopamine on membrane potential and synaptic currents. These results show that endogenous dopamine exerts a dual excitatory action on FS interneurons, by directly depolarizing them (through D1-like receptors) and by reducing their synaptic inhibition (through presynaptic D2-like receptors).
纹状体是多巴胺能神经支配的主要接受部位。纹状体投射神经元受胆碱能和γ-氨基丁酸能（GABAergic）中间神经元的控制。多巴胺对投射神经元和胆碱能中间神经元的作用已有描述。然而，其对GABA能中间神经元的作用仍不清楚。我们在体外利用细胞内记录研究了多巴胺对快速放电（FS）GABA能中间神经元的作用。浴槽应用多巴胺引发去极化，同时伴有膜输入电阻增加（在存在河豚毒素的情况下该效应持续存在）以及动作电位发放。这些效应可被D1样多巴胺受体激动剂SKF38393模拟，但不能被D2样激动剂喹吡罗模拟。诱发的皮质纹状体谷氨酸能突触电流不受多巴胺影响。相反，纹状体内刺激诱发的GABA能电流可被多巴胺和D2样激动剂（而非D1样激动剂）可逆性抑制。可卡因对膜电位和突触电流产生的效应与多巴胺类似。这些结果表明，内源性多巴胺对FS中间神经元发挥双重兴奋性作用，即通过直接使其去极化（通过D1样受体）以及通过减少其突触抑制（通过突触前D2样受体）。
