- 作者: Wan-Hsun Wu; Nai-Kuei Huang; Ching-Jiunn Tseng; Tsai-Hsin Yin; Che-Se Tung
- 作者服務機構: a Department of Physiology and Biophysics, b Graduate Institute of Life Sciences, and; c Department of Pharmacology, National; Defense Medical Center, Taipei, Taiwan; Republic of China
- 中文摘要: --
- 英文摘要: Amperozide, a novel atypical antipsychotic drug with few extrapyramidal side effects, is a strong serotonin2 (5-HT2) antagonist but has low affinity for dopa- mine receptors in vitro. The effect of amperozide on the dopaminergic synapse was studied with an in vivo microdialysis technique using anesthetized male Sprague-Dawley rats. Following implantation of dialysis probes into the stria- tum and nucleus accumbens (NuAc), amperozide was intravenously infused as six consecutive incremental doses (0.5, 0.5, 1.0, 2.0, 4.0 and 8.0 mg/kg) at inter- vals of 15 min. From the beginning of drug infusion, perfusates were collected in fractions every 30 min throughout a total period of 120 min. The samples were then immediately analyzed by high-performance liquid chromatography with electrochemical detection. Amperozide induced a dose-related elevation of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and 5-hydroxyindola- cetic acid (5-HIAA) levels in both areas. p-Chlorophenylalanine (pCPA) pre- treatment abolished the production of 5-HIAA in both areas and attenuated the amperozide-induced rise of DOPAC but not of dopamine. After pretreatment with an intravenous 5-HT3 antagonist, MDL 72222, the amperozide-induced changes in dopamine, DOPAC and 5-HIAA in both areas were lower than in the saline control group. Preliminary data showed that after pCPA pretreatment incremental concentrations of the 5-HT3 agonist 1-(m-chlorophenyl)-biguanide perfused via the probe also produced significant elevation of dopamine and DOPAC levels in these two areas. Taken together, these results suggest that amperozide may directly block 5-HT2 receptors in the striatum and NuAc, thereby enhancing 5-HT transmission. The enhanced 5-HT transmission may activate postsynpatic 5-HT3 receptors located on the dopaminergic terminals, leading to changes in dopamine transmission in these two areas.
- 中文關鍵字: --
- 英文關鍵字: Amperozide; Striatum; Nucleus accumbens; Serotonin; Dopamine; Transmission