Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus

Laurence L. Miller, Ahmad A. Altarifi, S. Stevens Negus

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. (PsycINFO Database Record

Original languageEnglish (US)
Pages (from-to)405-14
Number of pages10
JournalExperimental and Clinical Psychopharmacology
Volume23
Issue number5
DOIs
StatePublished - Oct 2015

Fingerprint

Self Stimulation
Morphine
Pain
Morphine Dependence
Opioid Analgesics
Acids
Therapeutics
Pain Management

Keywords

  • Drug abuse
  • Intracranial self-stimulation
  • Morphine
  • Opioid
  • Pain

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Psychiatry and Mental health

Cite this

Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus. / Miller, Laurence L.; Altarifi, Ahmad A.; Negus, S. Stevens.

In: Experimental and Clinical Psychopharmacology, Vol. 23, No. 5, 10.2015, p. 405-14.

Research output: Contribution to journalArticle

@article{cd9f43e076dd43dfa03eb9655dc4e56f,
title = "Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus",
abstract = "Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug na{\"i}ve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. (PsycINFO Database Record",
keywords = "Drug abuse, Intracranial self-stimulation, Morphine, Opioid, Pain",
author = "Miller, {Laurence L.} and Altarifi, {Ahmad A.} and Negus, {S. Stevens}",
note = "(c) 2015 APA, all rights reserved).",
year = "2015",
month = "10",
doi = "10.1037/pha0000042",
language = "English (US)",
volume = "23",
pages = "405--14",
journal = "Experimental and Clinical Psychopharmacology",
issn = "1064-1297",
publisher = "American Psychological Association Inc.",
number = "5",

}

TY - JOUR

T1 - Effects of repeated morphine on intracranial self-stimulation in male rats in the absence or presence of a noxious pain stimulus

AU - Miller, Laurence L.

AU - Altarifi, Ahmad A.

AU - Negus, S. Stevens

N1 - (c) 2015 APA, all rights reserved).

PY - 2015/10

Y1 - 2015/10

N2 - Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. (PsycINFO Database Record

AB - Research on opioid analgesics such as morphine suggests that expression of abuse-related effects increases with repeated exposure. Repeated exposure to opioids often occurs clinically in the context of pain management, and a major concern for clinicians is the risk of iatrogenic addiction and dependence in patients receiving opioids for treatment of pain. This study compared abuse-related morphine effects in male rats in an intracranial self-stimulation (ICSS) procedure after repeated treatment either with morphine alone or with morphine in combination with a repeated noxious stimulus (intraperitoneal administration of dilute acid). The study also permitted comparison of morphine potency and effectiveness to block acid-induced depression of ICSS (antinociception) and to produce enhanced facilitation of ICSS (abuse-related effect). There were 3 main findings. First, initial morphine exposure to drug naïve rats did not produce abuse-related ICSS facilitation. Second, repeated daily treatment with 3.2 mg/kg/day morphine for 6 days increased expression of ICSS facilitation. This occurred whether morphine was administered in the absence or presence of the noxious stimulus. Finally, a lower dose of 1.0 mg/kg/day morphine was sufficient to produce antinociception during repeated acid treatment, but this lower dose did not reliably increase abuse-related morphine effects. Taken together, these results suggest that prior morphine exposure can increase abuse liability of subsequent morphine treatments even when that morphine exposure occurs in the context of a pain state. However, it may be possible to relieve pain with relatively low morphine doses that do not produce increases in abuse-related morphine effects. (PsycINFO Database Record

KW - Drug abuse

KW - Intracranial self-stimulation

KW - Morphine

KW - Opioid

KW - Pain

UR - http://www.scopus.com/inward/record.url?scp=84942104059&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84942104059&partnerID=8YFLogxK

U2 - 10.1037/pha0000042

DO - 10.1037/pha0000042

M3 - Article

VL - 23

SP - 405

EP - 414

JO - Experimental and Clinical Psychopharmacology

JF - Experimental and Clinical Psychopharmacology

SN - 1064-1297

IS - 5

ER -