Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques

Michael R. Weed, Lucy M. Carruth, Robert John Adams, Nancy A Ator, Robert D Hienz

Research output: Contribution to journalArticle

Abstract

The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells.

Original languageEnglish (US)
Pages (from-to)250-259
Number of pages10
JournalJournal of NeuroImmune Pharmacology
Volume1
Issue number3
DOIs
StatePublished - Sep 2006

Fingerprint

Morphine Dependence
Macaca
Opiate Alkaloids
Morphine
Lymphocytes
Opioid-Related Disorders
Natural Killer Cells
Primates
Lymphocyte Subsets
Lymphocyte Count
Nutritional Status
Health Status
Monocytes
Immune System
Neutrophils
Pharmaceutical Preparations

Keywords

  • Immune lymphocyte
  • Macaque
  • Monocyte
  • Morphine dependence
  • Neutrophil
  • Withdrawal

ASJC Scopus subject areas

  • Pharmacology
  • Immunology and Allergy
  • Immunology
  • Neuroscience (miscellaneous)

Cite this

Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques. / Weed, Michael R.; Carruth, Lucy M.; Adams, Robert John; Ator, Nancy A; Hienz, Robert D.

In: Journal of NeuroImmune Pharmacology, Vol. 1, No. 3, 09.2006, p. 250-259.

Research output: Contribution to journalArticle

@article{0485a84e45c14b7aa12bd9f11815a2df,
title = "Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques",
abstract = "The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50{\%} reduction in numbers of CD4+, CD8+ and CD20+ cells.",
keywords = "Immune lymphocyte, Macaque, Monocyte, Morphine dependence, Neutrophil, Withdrawal",
author = "Weed, {Michael R.} and Carruth, {Lucy M.} and Adams, {Robert John} and Ator, {Nancy A} and Hienz, {Robert D}",
year = "2006",
month = "9",
doi = "10.1007/s11481-006-9029-z",
language = "English (US)",
volume = "1",
pages = "250--259",
journal = "Journal of NeuroImmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",
number = "3",

}

TY - JOUR

T1 - Morphine withdrawal dramatically reduces lymphocytes in morphine-dependent macaques

AU - Weed, Michael R.

AU - Carruth, Lucy M.

AU - Adams, Robert John

AU - Ator, Nancy A

AU - Hienz, Robert D

PY - 2006/9

Y1 - 2006/9

N2 - The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells.

AB - The immune effects of chronic opiate exposure and/or opiate withdrawal are not well understood. The results of human studies with opiate abusers are variable and may not be able to control for important factors such as subjects' drug histories, health and nutritional status. Nonhuman primate models are necessary to control these important factors. A model of opiate dependence in macaques was developed to study the effects of opiate dependence and withdrawal on measures of immune function. Four pigtailed macaques drank a mixture of morphine (20 mg/kg/session) and orange-flavored drink every 6 h for several months. During stable morphine dependence, absolute numbers of neutrophils, monocytes and lymphocytes did not change relative to pre-morphine levels. However, there was a significant decrease in the absolute number and percentage of natural killer (NK) cells in morphine dependence. Either precipitated withdrawal or abstinence for 24 h resulted in behavioral withdrawal signs in all animals. Absolute lymphocyte counts decreased and absolute netrophil counts increased significantly in withdrawal, relative to levels during morphine dependence. Lymphocyte subset (CD4+, CD8+, CD20+) cells were also decreased in absolute numbers with little change in their percentage distributions. There was, however, a significant increase in the percentage of NK cells in withdrawal relative to levels during morphine dependence. This study demonstrates the usefulness of voluntary oral self-dosing procedures for maintaining morphine dependence in nonhuman primates and demonstrates that the morphine withdrawal syndrome includes large alterations in blood parameters of immune system function, including nearly 50% reduction in numbers of CD4+, CD8+ and CD20+ cells.

KW - Immune lymphocyte

KW - Macaque

KW - Monocyte

KW - Morphine dependence

KW - Neutrophil

KW - Withdrawal

UR - http://www.scopus.com/inward/record.url?scp=33747342694&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33747342694&partnerID=8YFLogxK

U2 - 10.1007/s11481-006-9029-z

DO - 10.1007/s11481-006-9029-z

M3 - Article

VL - 1

SP - 250

EP - 259

JO - Journal of NeuroImmune Pharmacology

JF - Journal of NeuroImmune Pharmacology

SN - 1557-1890

IS - 3

ER -