期刊
JOURNAL OF PSYCHIATRIC RESEARCH
卷 139, 期 -, 页码 91-98出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.jpsychires.2021.05.042
关键词
Bipolar disorder; GSK38; Lisdexamfetamine; Lipid peroxidation; Oxidative stress; Ultrasonic vocalizations
类别
资金
- Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)
- Brazil-The Netherlands cooperation program CAPES-NUFFIC
- Deutsche Forschungsgemeinschaft (DFG) [SCHW 559/14-2]
- PPP program of the Deutsche Akademische Austauschdienst (DAAD) [57446778]
The study showed that andrographolide has antimanic-like effects on LDX-induced manic behaviors, which may be mediated through its antioxidant properties.
In rats, lisdexamfetamine (LDX) induces manic-like behaviors such as hyperlocomotion and increases in appetitive 50-kHz ultrasonic vocalizations (USV), which are prevented by antimanic drugs, such as lithium. Inhibition of glycogen synthase kinase 3 beta (GSK38) and antioxidant activity have been associated with antimanic effects. Thus, the aim of the present study was to evaluate the possible antimanic-like effects of andrographolide (ANDRO), a GSK38 inhibitor, on LDX-induced hyperlocomotion and 50-kHz USV increases. In addition, the effect of ANDRO was studied on LDX-induced oxidative stress. Lithium was used as positive control. Adult Wistar rats were treated with vehicle, lithium (100 mg/kg i.p., daily) or ANDRO (2 mg/kg i.p., 3 times a week) for 21 days. On the test day, either 10 mg/kg LDX or saline was administered i.p. and USV and locomotor activity were recorded. LDX administration increased the number of 50-kHz calls, as well as locomotor activity. Repeated treatment with lithium or ANDRO prevented these effects of LDX on 50-kHz USV and locomotor activity. LDX increased lipid peroxidation (LPO) levels in rat striatum and both lithium and ANDRO prevented this effect. LPO levels in rat striatum were positively correlated with increases in 50-kHz USV emission as well as hyperlocomotion. In conclusion, the present results indicate that ANDRO has antimanic-like effects, which may be mediated by its antioxidant properties.
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