Affective and neuroendocrine effects of withdrawal from chronic, long-acting opiate administration

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10 Scopus citations


Although the long-acting opiate methadone is commonly used to treat drug addiction, relatively little is known about the effects of withdrawal from this drug in preclinical models. The current study examined affective, neuroendocrine, and somatic signs of withdrawal from the longer-acting methadone derivative l-alpha-acetylmethydol (LAAM) in rats. Anxiety-like behavior during both spontaneous and antagonist-precipitated withdrawal was measured by potentiation of the startle reflex. Withdrawal elevated corticosterone and somatic signs and blunted circadian variations in baseline startle responding. In addition, fear to an explicit, Pavlovian conditioned stimulus (fear-potentiated startle) was enhanced. These data suggest that anxiety-like behavior as measured using potentiated startle responding does not emerge spontaneously during withdrawal from chronic opiate exposure - in contrast to withdrawal from acute drug exposure - but rather is manifested as exaggerated fear in response to explicit threat cues.

Original languageEnglish (US)
Pages (from-to)73-82
Number of pages10
JournalBrain Research
StatePublished - Nov 13 2013

Bibliographical note

Funding Information:
This project was funded by T32 DA07097 (K.L.H. and A.C.H.), DA018784, the University of Minnesota (JCG) , and the Minneapolis Medical Research Foundation Translational Addiction Research Program (ACH) . The authors thank Dr. Alicia Stachowski for statistical assistance.

Copyright 2013 Elsevier B.V., All rights reserved.


  • Acoustic startle
  • Corticosterone
  • Fear-potentiated startle
  • LAAM
  • Opiate dependence
  • Opiate withdrawal


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