Fusa Koichi, Saigusa Tadashi, Koshikawa Noriaki, Cools Alexander R
Department of Dental Anaesthesiology, Nihon University School of Dentistry, 1-8-13, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Eur J Pharmacol. 2002 Jul 19;448(2-3):143-50. doi: 10.1016/s0014-2999(02)01911-8.
Stimulation of dopamine D2-like receptors decreases extracellular dopamine in the dorsal striatum and the nucleus accumbens. It is unknown whether the role of these receptors differs from that of dopamine D3 receptors. It is also unknown to what extent the role of these two types of receptors varies across both structures. Using microdialysis, we therefore investigated whether intracerebrally administered quinpirole, a dopamine D2-like receptor agonist, and PD 128907, (S(+)-(4aR,10bR)-3,4,4a,10b-tetrahydro-4-propyl-2H,5H-[1]-benzopyrano[4,3-b]-1,4-oxazin-9-ol, a dopamine D3 receptor preferring agonist, differentially alter the tyrosine-induced increase of extracellular dopamine in the dorsal striatum and the nucleus accumbens, respectively. Perfusion of tyrosine (100 microM) into the dorsal striatum and the nucleus accumbens enhanced extracellular dopamine in a physiological manner in both areas. Infusion of the Na(+) channel blocker tetrodotoxin (2 microM) suppressed the enhanced level of dopamine derived from exogenous tyrosine in both brain areas. Infusion of the dopamine D2-like receptor agonist quinpirole at a concentration (1 nM), which alone did not affect basal extracellular dopamine, reduced tyrosine-enhanced extracellular dopamine when infused into the dorsal striatum, but not into the nucleus accumbens; the preferential dopamine D3 receptor agonist, PD 128907, had similar effects. Haloperidol, a dopamine D2-like receptor antagonist, given systemically at a dose, which alone did not significantly affect basal dopamine levels (10 nmol/kg i.p.), enhanced extracellular dopamine derived from exogenous tyrosine. This haloperidol treatment antagonized only the quinpirole-induced, but not the PD 128907-induced reduction in dopamine levels seen in tyrosine-treated rats. The results show that extracellular dopamine derived from exogenous tyrosine is under inhibitory control of presynaptic dopamine D2-like receptors in the dorsal striatum, but not in the nucleus accumbens; to what extent the same holds for dopamine D3 receptors remains to be proven. Future studies are required to elucidate whether the noted difference is absolute or not.
刺激多巴胺 D2 样受体可降低背侧纹状体和伏隔核中的细胞外多巴胺水平。尚不清楚这些受体的作用是否与多巴胺 D3 受体不同。这两种受体的作用在这两个结构中的差异程度也尚不清楚。因此，我们使用微透析技术研究了脑内注射喹吡罗（一种多巴胺 D2 样受体激动剂）和 PD 128907（S(+)-(4aR,10bR)-3,4,4a,10b-四氢-4-丙基-2H,5H-[1]-苯并吡喃[4,3-b]-1,4-恶嗪-9-醇，一种更倾向于多巴胺 D3 受体的激动剂）是否分别差异性地改变酪氨酸诱导的背侧纹状体和伏隔核中细胞外多巴胺的增加。向背侧纹状体和伏隔核灌注酪氨酸（100 microM）以生理方式增强了这两个区域的细胞外多巴胺。注入 Na(+)通道阻滞剂河豚毒素（2 microM）抑制了两个脑区中外源性酪氨酸衍生的多巴胺增强水平。注入浓度为 1 nM 的多巴胺 D2 样受体激动剂喹吡罗（其单独不影响基础细胞外多巴胺），当注入背侧纹状体时可降低酪氨酸增强的细胞外多巴胺，但注入伏隔核时则无此作用；更倾向于多巴胺 D3 受体的激动剂 PD 128907 具有类似作用。氟哌啶醇，一种多巴胺 D2 样受体拮抗剂，以单独不显著影响基础多巴胺水平的剂量（10 nmol/kg 腹腔注射）全身给药，增强了外源性酪氨酸衍生的细胞外多巴胺。这种氟哌啶醇治疗仅拮抗了酪氨酸处理大鼠中喹吡罗诱导的多巴胺水平降低，而不拮抗 PD 128907 诱导的多巴胺水平降低。结果表明，外源性酪氨酸衍生的细胞外多巴胺在背侧纹状体中受到突触前多巴胺 D2 样受体的抑制性控制，但在伏隔核中并非如此；多巴胺 D3 受体是否同样如此仍有待证实。未来的研究需要阐明所指出的差异是否是绝对的。
J Pharmacol Exp Ther. 2005-7
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