伊博格碱局部作用对多巴胺释放的神经药理学特征

Neuropharmacological characterization of local ibogaine effects on dopamine release.

作者信息

Reid M S, Hsu K, Souza K H, Broderick P A, Berger S P

机构信息

UCSF/VAMC Substance Abuse Research 116W, USA.

出版信息

J Neural Transm (Vienna). 1996;103(8-9):967-85. doi: 10.1007/BF01291787.

DOI:10.1007/BF01291787

PMID:9013390

Abstract

Local perfusion with ibogaine (10(-6) M-10(-3) M) via microdialysis probes in the nucleus accumbens or striatum of rats produced a biphasic dose-response effect on extracellular dopamine levels. Lower doses (10(-6) M-10(-4) M) produced a decrease while higher doses (5 x 10(-4) M-10(-3) M) produced an increase in dopamine levels. Dihydroxyphenylacetic acid (DOPAC) levels were not effected. Naloxone (10(-6) M) and norbinaltorphimine (10(-6) M-10(-5) M) did not affect dopamine levels, but when co-administered with ibogaine (10(-4) M) blocked the decrease in dopamine levels produced by ibogaine. Ibogaine (10(-3) M) stimulation of dopamine levels in the striatum was calcium independent and not blocked by tetrodotoxin (10(-5) M). Pretreatment with cocaine (15 mg/kg), reserpine (5 mg/kg) or alpha-methyl-para-tyrosine (250 mg/kg) given intraperitoneally significantly reduced ibogaine (10(-3)M) stimulation of striatal dopamine levels. In striatal synaptosomes, both ibogaine and harmaline (10(-7)-10(-4) M) produced dose-dependent inhibition of [3H]-dopamine uptake. These findings suggest that ibogaine has both inhibitory and stimulatory effects on dopamine release at the level of the nerve terminal. It is suggested that the inhibitory effect is mediated by kappa opiate receptors while the stimulatory effect is mediated by interaction with the dopamine uptake transporter.

摘要

通过微透析探针向大鼠伏隔核或纹状体局部灌注伊波加因（10⁻⁶ M - 10⁻³ M），对细胞外多巴胺水平产生双相剂量反应效应。较低剂量（10⁻⁶ M - 10⁻⁴ M）导致多巴胺水平降低，而较高剂量（5×10⁻⁴ M - 10⁻³ M）则使多巴胺水平升高。二羟基苯乙酸（DOPAC）水平未受影响。纳洛酮（10⁻⁶ M）和去甲二氢吗啡酮（10⁻⁶ M - 10⁻⁵ M）不影响多巴胺水平，但与伊波加因（10⁻⁴ M）共同给药时，可阻断伊波加因引起的多巴胺水平降低。伊波加因（10⁻³ M）对纹状体多巴胺水平的刺激不依赖于钙，且不受河豚毒素（10⁻⁵ M）阻断。腹腔注射可卡因（15 mg/kg）、利血平（5 mg/kg）或α-甲基-对酪氨酸（250 mg/kg）预处理可显著降低伊波加因（10⁻³ M）对纹状体多巴胺水平的刺激。在纹状体突触体中，伊波加因和哈尔满（10⁻⁷ - 10⁻⁴ M）均产生剂量依赖性的[³H] - 多巴胺摄取抑制作用。这些发现表明，伊波加因在神经末梢水平对多巴胺释放具有抑制和刺激作用。提示抑制作用由κ阿片受体介导，而刺激作用由与多巴胺摄取转运体的相互作用介导。