Neonatal fluoxetine exposure induced depression-like behaviors in adult Kunming mice and the antidepressant-like effect of agmatine.
- Author:
Xian-Zhong JIANG
1
;
Yan-Qin LIU
;
You-Zhi ZHANG
;
Li-Ming ZHANG
;
Jin LI
;
Yun-Feng LI
Author Information
1. Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
- Publication Type:Journal Article
- MeSH:
Agmatine;
pharmacology;
Animals;
Antidepressive Agents;
pharmacology;
Depressive Disorder;
chemically induced;
Disease Models, Animal;
Female;
Fluoxetine;
administration & dosage;
adverse effects;
Male;
Mice;
Mice, Inbred Strains
- From:
Acta Pharmaceutica Sinica
2009;44(7):716-721
- CountryChina
- Language:Chinese
-
Abstract:
This study is to explore a behavioral and pathological model for depression in mice, and evaluate the anti-depressant-like effect of agmatine. Neonatal Kunming mice were treated with fluoxetine (10 mg x kg(-1), ip, qd) for 17 d (between day 4 and 21 after birth), and then the mice were normally housed till being adult (about 10 weeks after birth). The behaviors of the mice were measured by using open-field test, novelty suppressed feeding test and tail-suspension test. Hippocampal adenylate cyclase (AC) activity was measured by radioimmunoassay. Neonatal exposure to fluoxetine induced a "depression-like" behaviors in the adult mice, shown as the decreased locomotor activity, increased feeding latency and immobility time in the open-field test, novelty suppressed feeding test, and tail-suspension test, respectively. Chronic agmatine treatment (10 mg x kg(-1), ig, bid) for 3 weeks significantly increased the locomotor activity, and decreased the feeding latency in the neonatal fluoxetine exposed mice. Furthermore, single treatment with agmatine (40 mg x kg(-1), ig) also decreased the immobility time in the tail-suspension test, and increased the hippocampal AC activity in the mice. These results indicate that neonatal exposure to fluoxetine induces depressive-like behaviors in the adult mice. Agmatine reverses these behaviors, which may be closely related to the enhancement of the hippocampal AC activity.