REGIONAL c-Fos AND FosB/ΔFosB EXPRESSION ASSOCIATED WITH CHRONIC METHAMPHETAMINE SELF-ADMINISTRATION AND METHAMPHETAMINE-SEEKING BEHAVIOR IN RATS

被引：45

作者：

Cornish, J. L. ^{[2
]}

Hunt, G. E. ^{[1
]}

Robins, L. ^{[3
]}

McGregor, I. S. ^{[3
]}

机构：

[1] Univ Sydney, Sydney Med Sch, Concord Hosp, Discipline Psychiat, Concord, NSW 2139, Australia

[2] Macquarie Univ, Dept Psychol, Sydney, NSW 2109, Australia

[3] Univ Sydney, Dept Psychol, Sydney, NSW 2006, Australia

来源：

NEUROSCIENCE | 2012年 / 206卷

基金：

英国医学研究理事会;

关键词：

methamphetamine; self-administration; c-Fos; FosB; orexin; addiction; VENTRAL TEGMENTAL AREA; HYPOTHALAMIC OREXIN NEURONS; EARLY GENE-EXPRESSION; DELTA-FOSB; PREFRONTAL CORTEX; SUBTHALAMIC NUCLEUS; BRAIN-STIMULATION; STRIATAL NEURONS; ALCOHOL-SEEKING; GABAERGIC TAIL;

D O I：

10.1016/j.neuroscience.2012.01.004

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

The regional expression of the transcription factors c-Fos and FosB/Delta FosB was examined in rats given acute exposure to intravenous methamphetamine (METH) or repeated intravenous METH self-administration. One group of rats self-administered METH via lever pressing in 2 h sessions every day for 3 weeks and on a final test day received self-administered METH as usual. A second group with the same METH self-administration history received saline infusions on the test day, to induce drug-seeking behavior. Other rats were trained with infusions of intravenous saline that were yoked to the passive delivery of METH in the other two groups. On test day, half of these yoked rats received passive METH infusions for the first time, whereas the others received saline as usual. The results showed that acute METH produced a characteristic signature of Fos expression with elevations in striatal, cortical, and extended amygdala regions. Importantly, rats with a 3-week history of METH self-administration displayed similar regional Fos expression to rats receiving METH for the first time. Rats seeking, but not receiving, METH on the test day had augmented Fos in the lateral hypothalamus, septum, and vertical limb of the diagonal band of Broca, suggesting a primary role for these regions in METH-seeking behavior. Both acute and chronic METH activated orexin-positive cells in the perifornical area of the hypothalamus. FosB/Delta FosB was elevated in the lateral hypothalamus, posterior ventral tegmental area, central amygdala, and dorsal raphe of all the rats with a history of METH self-administration. This occurred regardless of whether they received METH on test day, suggesting presence of the long-lived FosB isoform, Delta FosB. Overall, these results show persistent upregulated regional brain Fos and FosB/Delta FosB expression with chronic METH self-administration and indicate a role for the lateral hypothalamus and lateral septum in METH-seeking behavior. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：100 / 114

页数：15

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