期刊
BIOLOGICAL PSYCHIATRY
卷 63, 期 11, 页码 1007-1012出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.biopsych.2007.10.018
关键词
anxiety; cocaine; disulfiram; dopamine P-hydroxylase; elevated plus maze; norepinephrine
资金
- NIDA NIH HHS [F31 DA019746, T32 DA015040, R01 DA017963-01A2, T32 DA015040-04, R01 DA017963, R03 DA019849-01, DA019746, R01 DA017963-03, R03 DA019849, DA019849, F31 DA019746-01A2, DA015040, R01 DA017963-02, DA017963] Funding Source: Medline
Background: Cocaine is a widely abused psychostimulant that has both rewarding and aversive properties. While the mechanisms underlying cocaine's rewarding effects have been studied extensively, less attention has been paid to the unpleasant behavioral states induced by cocaine, such as anxiety. Methods: In this study, we evaluated the performance of dopamine P-hydroxylase knockout (Dbh -/-) mice, which lack norepinephrine (NE), in the elevated plus maze (EPM) to examine the contribution of noradrenergic signaling to cocaine-induced anxiety. Results: We found that cocaine dose-dependently increased anxiety-like behavior in control (Dbh +/-)mice, as measured by a decrease in open arm exploration. The Dbh -/- mice had normal baseline performance in the EPM but were completely resistant to the anxiogenic effects of cocaine. Cocaine-incluced anxiety was also attenuated in Dbh +/- mice following administration of disulfiram, a dopamine P-hydroxylase (DBH) inhibitor. In experiments using specific adrenergic antagonists, we found that pretreatment with the P-adrenergic receptor antagonist propranolol blocked cocaine-induced anxiety-like behavior in Dbh +/- and wild-type C57BL6/J mice, while the a, antagonist prazosin and the alpha(2) antagonist yohimbine had no effect. Conclusions: These results indicate that noradrenergic signaling via P-adrenergic receptors is required for cocaine-induced anxiety in mice.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据