Effects of novel anxiolytic 4-butyl-alpha-agarofuran on levels of monoamine neurotransmitters in rats.
4-butyl-alpha-agarofuran (AF-5) is a new compound derived from alpha-agarofuran, a constituent extracted from Aquillaria agallocha Roxb. Our previous research has shown that AF-5 has significant antianxiety activity in several animal models. In this study, an antianxiety effect was observed in a social interaction test after acute treatment with AF-5 (0.5-4.0 mg/kg, i.p.) in rats. Using high-performance liquid chromatography (HPLC)-electrochemical detection (ECD), we further investigated the effects of AF-5 on monoamine neurotransmitters both in rat brain tissues and in striatum dialysates. After acute administration of AF-5 (5.0 mg/kg, i.p.), serotonin (5-hydroxytryptamine, 5-HT) tissue levels significantly decreased by 26.3%, 30.4%, and 17.4% of the vehicle-control levels, in the striatum, cortex, and midbrain, respectively. The dopamine level decreased by 34.7% in the striatum and 19.0% in the midbrain, while in the hypothalamus, it increased to 156.6%. The epinephrine level decreased by 34.6% in the cortex. In cerebral microdialysis perfusates from rat striatum, the extracellular dopamine level declined stepwise after treatment with AF-5 (10.0 mg/kg, i.p.). By 200 min postinjection, the dopamine level reached a minimum, about 40% of the baseline value. At the same time, the extracellular levels of 5-hydroxyindolacetic acid, 3-4-dihydroxyphenylacetic acid, and homovanillic acid increased significantly, the maximum values were 150%, 145%, and 175% above baseline, respectively. This study suggests that AF-5 is a potent anxiolytic agent, and that its beneficial action may be related to its effects on central monoamine neurotransmitters.
Zhang
Yi
Y
Department of Pharmacology, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, 1 Xian Nong Tan Street, Beijing 100050, China.
Wang
Weijun
W
Zhang
Jianjun
J
D000818:Animals; D014151:Anti-Anxiety Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001007:Anxiety / Q000188:drug therapy / Q000378:metabolism; D015306:Biogenic Monoamines / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006575:Heterocyclic Compounds, 3-Ring / Q000494:pharmacology* / Q000627:therapeutic use; D007398:Interpersonal Relations; D008297:Male; D051381:Rats; D017208:Rats, Wistar
C481920:AF-5 compound; D014151:Anti-Anxiety Agents; D015306:Biogenic Monoamines; D006575:Heterocyclic Compounds, 3-Ring