[Neonatal fluoxetine exposure induced depression-like behaviors in adult Kunming mice and the antidepressant-like effect of agmatine].
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.
Jiang
Xian-Zhong
XZ
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Liu
Yan-Qin
YQ
Zhang
You-Zhi
YZ
Zhang
Li-Ming
LM
Li
Jin
J
Li
Yun-Feng
YF
D000376:Agmatine / Q000494:pharmacology*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D003866:Depressive Disorder / Q000139:chemically induced*; D004195:Disease Models, Animal; D005260:Female; D005473:Fluoxetine / Q000008:administration & dosage / Q000009:adverse effects*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains
D000928:Antidepressive Agents; D005473:Fluoxetine; D000376:Agmatine