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Journal article
Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain
Progress in neuro-psychopharmacology & biological psychiatry, v 32(4), pp 1048-1056
15 May 2008
PMID: 18367303
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Abstract
The administration of low dose opioid antagonists has been explored as a potential means of detoxification in opiate dependence. Previous results from our laboratory have shown that concurrent administration of low dose naltrexone in the drinking water of rats implanted with subcutaneous morphine pellets attenuates behavioral and biochemical signs of withdrawal in brainstem noradrenergic nuclei. Noradrenergic projections originating from the nucleus tractus solitarius (NTS) and the locus coeruleus (LC) have previously been shown to be important neural substrates involved in the somatic expression of opiate withdrawal. The hypothesis that low dose naltrexone treatment attenuates noradrenergic hyperactivity typically associated with opiate withdrawal was examined in the present study by assessing norepinephrine tissue content and norepinephrine efflux using in vivo microdialysis coupled to high performance liquid chromatography (HPLC) with electrochemical detection (ED). The frontal cortex (FC), amygdala, bed nucleus of the stria terminalis (BNST) and cerebellum were analyzed for tissue content of norepinephrine following withdrawal in morphine dependent rats. Naltrexone-precipitated withdrawal elicited a significant decrease in tissue content of norepinephrine in the BNST and amygdala. This decrease was significantly attenuated in the BNST of rats that received low dose naltrexone pre-treatment compared to controls. No significant difference was observed in the other brain regions examined. In a separate group of rats, norepinephrine efflux was assessed with in vivo microdialysis in the BNST or the FC of morphine dependent rats or placebo treated rats subjected to naltrexone-precipitated withdrawal that received either naltrexone in their drinking water (5 mg/L) or unadulterated water. Following baseline dialysate collection, withdrawal was precipitated by injection of naltrexone and sample collection continued for an additional 4 h. At the end of the experiment, animals were transcardially perfused and the brains were removed for verification of probe placement. Low dose naltrexone pre-treatment significantly attenuated withdrawal-induced increases of extracellular norepinephrine in the BNST, with a smaller effect in the FC. These findings suggest that alterations in norepinephrine release associated with withdrawal may be attenuated in forebrain targets of noradrenergic brainstem, neurons that may underlie reduced behavioral signs of withdrawal following low dose naltrexone administration. Published by Elsevier Inc.
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Details
- Title
- Low dose naltrexone administration in morphine dependent rats attenuates withdrawal-induced norepinephrine efflux in forebrain
- Creators
- Elisabeth J. Van Bockstaele - Jefferson Hospital for NeuroscienceYaping Qian - Jefferson Hospital for NeuroscienceRobert C. Sterling - Thomas Jefferson UniversityMichelle E. Page - Jefferson Hospital for Neuroscience
- Publication Details
- Progress in neuro-psychopharmacology & biological psychiatry, v 32(4), pp 1048-1056
- Publisher
- Elsevier
- Number of pages
- 9
- Grant note
- K02 DA015395; DA15123; K02 DA015395-05; R21 DA015123; DA15395; R21 DA015123-03 / NIDA NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA) K02DA015395 / NATIONAL INSTITUTE ON DRUG ABUSE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute on Drug Abuse (NIDA); European Commission
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Graduate School - Dean's Office; Pharmacology and Physiology
- Web of Science ID
- WOS:000256570400020
- Scopus ID
- 2-s2.0-42949127589
- Other Identifier
- 991021903295404721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Clinical Neurology
- Neurosciences
- Pharmacology & Pharmacy
- Psychiatry