Reduced emotional and corticosterone responses to stress in μ-opioid receptor knockout mice

NEUROPHARMACOLOGY

卷:58

Article; Proceedings Paper

Ide, Soichiro^1,2  Sora, Ichiro³  Ikeda, Kazutaka⁴  Minami, Masabumi²  Uhl, George R.⁵  Ishihara, Kumatoshi¹ 

[1] Hiroshima Int Univ, Neuropharmacol Lab, Fac Pharmaceut Sci, Hirokoshingai, Kure 7370112, Japan

[2] Hokkaido Univ, Dept Pharmacol, Grad Sch Pharmaceut Sci, Sapporo, Hokkaido 0600812, Japan

[3] Tohoku Univ, Grad Sch Med, Dept Biol Psychiat, Sendai, Miyagi 9808574, Japan

[4] Tokyo Inst Psychiat, Div Psychobiol, Tokyo 1568585, Japan

[5] NIDA, Baltimore, MD 21224 USA

关键词: mu-Opioid receptor;    Knockout mouse;    Corticosterone;    Stress;    Anxiety;    Depression;   

DOI  :  10.1016/j.neuropharm.2009.07.005

来源: Elsevier

【 摘 要 】

The detailed mechanisms of emotional modulation in the nervous system by opioids remain to be elucidated, although the opioid system is well known to play important roles in the mechanisms of analgesia and drug dependence. in the present study, we conducted behavioral tests of anxiety and depression and measured corticosterone concentrations in both male and female mu-opioid receptor knockout (MOP-KO) mice to reveal the involvement of mu-opioid receptors in stress-induced emotional responses. MCP-KO mice entered more and spent more time in the open arms of the elevated plus maze compared with wild-type mice. MOP-KO mice also displayed significantly decreased immobility in a 15 min tail-suspension test compared with wild-type mice. Similarly, MOP-KO mice exhibited significantly decreased immobility on days 2, 3, and 4 in a 6 min forced swim test conducted for 5 consecutive days. The increase in plasma corticosterone concentration induced by tail-suspension, repeated forced swim, or restraint stress was reduced in MOP-KO mice compared with wild-type mice. Corticosterone levels were not different between wild-type and MOP-KO mice before stress exposure. In contrast, although female mice tended to exhibit fewer anxiety-like responses in the tail-suspension test in both genotypes, no significant gender differences were observed in stress-induced emotional responses. These results suggest that MOPs play an important facilitatory role in emotional responses to stress, including anxiety- and depression-like behavior and corticosterone levels. (C) 2009 Elsevier Ltd. All rights reserved.

【 授权许可】

Free