Noradrenaline in the ventral forebrain is critical for opiate withdrawal-induced aversion

被引:369
作者
Delfs, JM [1 ]
Zhu, Y [1 ]
Druhan, JP [1 ]
Aston-Jones, G [1 ]
机构
[1] Univ Penn, Sch Med, Dept Psychiat, VA Med Ctr 151, Philadelphia, PA 19104 USA
关键词
D O I
10.1038/35000212
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Cessation of drug use in chronic opiate abusers produces a severe withdrawal syndrome that is highly aversive, and avoidance of withdrawal or associated stimuli is a major factor contributing to opiate abuse(1,2). Increased noradrenaline in the brain has long been implicated in opiate withdrawal(3), but it has not been clear which noradrenergic systems are invoked. Here we show that microinjection of beta-noradrenergic-receptor antagonists, or of an alpha 2-receptor agonist, into the bed nucleus of the stria terminalis (BNST) in rats markedly attenuates opiate-withdrawal-induced conditioned place aversion, Immunohistochemical studies revealed that numerous BNST-projecting cells in the A1 and A2 noradrenergic cell groups of the caudal medulla were activated during withdrawal Lesion of these ascending medullary projections also greatly reduced opiate-withdrawal-induced place aversion. whereas lesion of locus coeruleus noradrenergic projections had no effect on opiate-withdrawal behaviour. We conclude that noradrenergic inputs to the BNST from the caudal medulla are critically involved in the aversiveness of opiate withdrawal.
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页码:430 / 434
页数:5
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