Serra Pier Andrea, Susini Giuseppe, Rocchitta Gaia, Migheli Rossana, Dessanti Giuseppina, Miele Egidio, Desole Maria Speranza, Miele Maddalena
Department of Pharmacology, University of Sassari, viale S Pietro 43B, 07100 Sassari, Italy.
Neurosci Lett. 2003 Jun 19;344(1):9-12. doi: 10.1016/s0304-3940(03)00395-1.
The effects of either intraperitoneally (i.p.) or intrastriatally administered sufentanil on the release and metabolism of dopamine (DA) in the rat striatum were evaluated using in vivo microdialysis. Dialysate concentrations of DA and its acidic metabolites dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) were increased following i.p. administration of either clinical anesthetic (20 microg/kg) or clinical analgesic (1 microg/kg) sufentanil doses. In addition, sufentanil also increased uric acid concentrations. In contrast, dialysate ascorbic acid and glutamate concentrations were unaffected. Intrastriatal infusion of sufentanil (250 nM) induced only a short lasting decrease in dialysate DA. Subcutaneous naloxone (1.0 mg/kg) abolished sufentanil-induced increases in dialysate DA, DOPAC+HVA and uric acid; however, naloxone (0.1 mM) failed to affect these increases when infused intrastriatally. These results demonstrate that sufentanil, at clinical doses, increases striatal DA release and oxidative metabolism of both DA and xanthine acting at extrastriatal sites with a mu-receptor-mediated mechanism.
采用体内微透析技术评估腹腔注射(i.p.)或纹状体内注射舒芬太尼对大鼠纹状体内多巴胺(DA)释放及代谢的影响。腹腔注射临床麻醉剂量(20微克/千克)或临床镇痛剂量(1微克/千克)的舒芬太尼后,透析液中DA及其酸性代谢产物二羟基苯乙酸(DOPAC)和高香草酸(HVA)的浓度升高。此外,舒芬太尼还使尿酸浓度升高。相比之下,透析液中抗坏血酸和谷氨酸浓度未受影响。纹状体内注射舒芬太尼(250纳摩尔)仅引起透析液中DA短暂下降。皮下注射纳洛酮(1.0毫克/千克)可消除舒芬太尼引起的透析液中DA、DOPAC+HVA及尿酸的升高;然而,纹状体内注射纳洛酮(0.1毫摩尔)时未能影响这些升高。这些结果表明,临床剂量的舒芬太尼通过μ受体介导机制作用于纹状体以外部位,增加纹状体DA释放以及DA和黄嘌呤的氧化代谢。