Fluoxetine pretreatment promotes neuronal survival and maturation after auditory fear conditioning in the rat amygdala

Lizhu Jiang; Chen Liu; Jianbin Tong; Rongrong Mao; Dan Chen; Hui Wang; Jufang Huang; Lingjiang Li

doi:10.1371/journal.pone.0089147

Fluoxetine pretreatment promotes neuronal survival and maturation after auditory fear conditioning in the rat amygdala

PLoS One. 2014 Feb 13;9(2):e89147. doi: 10.1371/journal.pone.0089147. eCollection 2014.

Authors

Lizhu Jiang¹, Chen Liu², Jianbin Tong³, Rongrong Mao⁴, Dan Chen², Hui Wang², Jufang Huang², Lingjiang Li⁵

Affiliations

¹ Mental Health Institute, The Second Xiangya Hospital, and Key Lab of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, China ; Department of neuropsychopathy, clinical medical school, Dali University, Dali, China.
² Department of Anatomy and Neurobiology, School of Basic Medical Sciences, Central South University, Changsha, China.
³ The Third Xiangya Hospital, Central South University, Changsha, China.
⁴ Key Lab of Animal Models and Human Disease Mechanisms, Kunming Institute of Zoology, the Chinese Academy of Sciences, Kunming, China.
⁵ Mental Health Institute, The Second Xiangya Hospital, and Key Lab of Psychiatry and Mental Health of Hunan Province, Central South University, Changsha, China.

Abstract

The amygdala is a critical brain region for auditory fear conditioning, which is a stressful condition for experimental rats. Adult neurogenesis in the dentate gyrus (DG) of the hippocampus, known to be sensitive to behavioral stress and treatment of the antidepressant fluoxetine (FLX), is involved in the formation of hippocampus-dependent memories. Here, we investigated whether neurogenesis also occurs in the amygdala and contributes to auditory fear memory. In rats showing persistent auditory fear memory following fear conditioning, we found that the survival of new-born cells and the number of new-born cells that differentiated into mature neurons labeled by BrdU and NeuN decreased in the amygdala, but the number of cells that developed into astrocytes labeled by BrdU and GFAP increased. Chronic pretreatment with FLX partially rescued the reduction in neurogenesis in the amygdala and slightly suppressed the maintenance of the long-lasting auditory fear memory 30 days after the fear conditioning. The present results suggest that adult neurogenesis in the amygdala is sensitive to antidepressant treatment and may weaken long-lasting auditory fear memory.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Acoustic Stimulation
Amygdala / cytology
Amygdala / drug effects*
Amygdala / physiology
Animals
Antidepressive Agents, Second-Generation / pharmacology*
Astrocytes / cytology
Astrocytes / drug effects
Astrocytes / physiology
Bromodeoxyuridine
Cell Differentiation / drug effects
Cell Proliferation / drug effects
Cell Survival / drug effects
Conditioning, Classical / drug effects
Conditioning, Classical / physiology
Fear / drug effects*
Fear / psychology
Fluoxetine / pharmacology*
Hippocampus / cytology
Hippocampus / drug effects
Hippocampus / physiology
Male
Neurogenesis / drug effects
Neurogenesis / physiology
Neurons / cytology
Neurons / drug effects*
Neurons / physiology
Rats
Rats, Sprague-Dawley

Substances

Antidepressive Agents, Second-Generation
Fluoxetine
Bromodeoxyuridine

Grants and funding

This work was supported by grants from the National Natural Science Foundation of China (3086008 to Lizhu Jiang; 31100786 to Rongrong Mao; 930830046, 81171286, and 91232714 to Lingjiang Li), the National 973 Program of China (2009CB918303 to Lingjiang Li), and the Program of the Chinese Ministry of Education (20090162110011 to Lingjiang Li). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.