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

J. M. Delfs, Y. Zhu, J. P. Druhan and G. Aston-Jones ()
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J. M. Delfs: University of Pennsylvania School of Medicine
Y. Zhu: University of Pennsylvania School of Medicine
J. P. Druhan: University of Pennsylvania School of Medicine
G. Aston-Jones: University of Pennsylvania School of Medicine

Nature, 2000, vol. 403, issue 6768, 430-434

Abstract: Abstract 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 abuse1,2. Increased noradrenaline in the brain has long been implicated in opiate withdrawal3, but it has not been clear which noradrenergic systems are involved. Here we show that microinjection of β-noradrenergic-receptor antagonists, or of an α2-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.

Date: 2000
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DOI: 10.1038/35000212

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