Chronic naltrexone supersensitizes the reinforcing and locomotor-activating effects of morphine

M. T. Bardo, Janet Neisewander

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Rats were implanted for 10 days with a slow-release naltrexone pellet and then the pellet was removed. Sham-control animals were treated similarly, except no pellet was implanted. One day after pellet removal or sham treatment, animals were assessed for morphine-induced conditioned place preference (CPP) or locomotor activity. CPP was evident in sham animals following two conditioning trials using 5 mg/kg subcutaneous morphine (Experiment 1) and following one conditioning trial using 8 mg/kg intravenous morphine (Experiment 2). Animals conditioned while implanted with a naltrexone pellet showed no morphine-induced CPP. More important, one day after pellet removal, naltrexone-pretreated animals given one conditioning trial with 5 mg/kg intravenous morphine displayed a greater preference for morphine-associated cues relative to sham animals given morphine (Experiment 3 and 4). This single IV morphine dose was insufficient to produce CPP in sham animals, suggesting that naltrexone-induced supersensitization may only be evident at a morphine dose below the reinforcing threshold in control animals. Further, chronic naltrexone potentiated the locomotor-activating effect of 2 mg/kg subcutaneous morphine but not of either 1 or 5 mg/kg morphine (Experiment 5). Behavioral supersensitization assessed by morphine-induced locomotor activation was transient, as it was evident one day, but not either three or 10 days following pellet removal (Experiment 6). These results confirm the functional significance of opiate receptor up-regulation following chronic opioid blockade.

Original languageEnglish (US)
Pages (from-to)267-273
Number of pages7
JournalPharmacology, Biochemistry and Behavior
Volume28
Issue number2
DOIs
StatePublished - 1987
Externally publishedYes

Fingerprint

Naltrexone
Morphine
Animals
Experiments
Opioid Receptors
Locomotion
Opioid Analgesics
Cues
Rats
Up-Regulation
Chemical activation

Keywords

  • Conditioned place preference
  • Locomotor activity
  • Morphine
  • Naltrexone
  • Opiate receptor
  • Receptor up-regulation

ASJC Scopus subject areas

  • Biochemistry
  • Behavioral Neuroscience
  • Pharmacology

Cite this

Chronic naltrexone supersensitizes the reinforcing and locomotor-activating effects of morphine. / Bardo, M. T.; Neisewander, Janet.

In: Pharmacology, Biochemistry and Behavior, Vol. 28, No. 2, 1987, p. 267-273.

Research output: Contribution to journalArticle

@article{b542944e02804fbfbbbc925ed5edd053,
title = "Chronic naltrexone supersensitizes the reinforcing and locomotor-activating effects of morphine",
abstract = "Rats were implanted for 10 days with a slow-release naltrexone pellet and then the pellet was removed. Sham-control animals were treated similarly, except no pellet was implanted. One day after pellet removal or sham treatment, animals were assessed for morphine-induced conditioned place preference (CPP) or locomotor activity. CPP was evident in sham animals following two conditioning trials using 5 mg/kg subcutaneous morphine (Experiment 1) and following one conditioning trial using 8 mg/kg intravenous morphine (Experiment 2). Animals conditioned while implanted with a naltrexone pellet showed no morphine-induced CPP. More important, one day after pellet removal, naltrexone-pretreated animals given one conditioning trial with 5 mg/kg intravenous morphine displayed a greater preference for morphine-associated cues relative to sham animals given morphine (Experiment 3 and 4). This single IV morphine dose was insufficient to produce CPP in sham animals, suggesting that naltrexone-induced supersensitization may only be evident at a morphine dose below the reinforcing threshold in control animals. Further, chronic naltrexone potentiated the locomotor-activating effect of 2 mg/kg subcutaneous morphine but not of either 1 or 5 mg/kg morphine (Experiment 5). Behavioral supersensitization assessed by morphine-induced locomotor activation was transient, as it was evident one day, but not either three or 10 days following pellet removal (Experiment 6). These results confirm the functional significance of opiate receptor up-regulation following chronic opioid blockade.",
keywords = "Conditioned place preference, Locomotor activity, Morphine, Naltrexone, Opiate receptor, Receptor up-regulation",
author = "Bardo, {M. T.} and Janet Neisewander",
year = "1987",
doi = "10.1016/0091-3057(87)90224-3",
language = "English (US)",
volume = "28",
pages = "267--273",
journal = "Pharmacology Biochemistry and Behavior",
issn = "0091-3057",
publisher = "Elsevier Inc.",
number = "2",

}

TY - JOUR

T1 - Chronic naltrexone supersensitizes the reinforcing and locomotor-activating effects of morphine

AU - Bardo, M. T.

AU - Neisewander, Janet

PY - 1987

Y1 - 1987

N2 - Rats were implanted for 10 days with a slow-release naltrexone pellet and then the pellet was removed. Sham-control animals were treated similarly, except no pellet was implanted. One day after pellet removal or sham treatment, animals were assessed for morphine-induced conditioned place preference (CPP) or locomotor activity. CPP was evident in sham animals following two conditioning trials using 5 mg/kg subcutaneous morphine (Experiment 1) and following one conditioning trial using 8 mg/kg intravenous morphine (Experiment 2). Animals conditioned while implanted with a naltrexone pellet showed no morphine-induced CPP. More important, one day after pellet removal, naltrexone-pretreated animals given one conditioning trial with 5 mg/kg intravenous morphine displayed a greater preference for morphine-associated cues relative to sham animals given morphine (Experiment 3 and 4). This single IV morphine dose was insufficient to produce CPP in sham animals, suggesting that naltrexone-induced supersensitization may only be evident at a morphine dose below the reinforcing threshold in control animals. Further, chronic naltrexone potentiated the locomotor-activating effect of 2 mg/kg subcutaneous morphine but not of either 1 or 5 mg/kg morphine (Experiment 5). Behavioral supersensitization assessed by morphine-induced locomotor activation was transient, as it was evident one day, but not either three or 10 days following pellet removal (Experiment 6). These results confirm the functional significance of opiate receptor up-regulation following chronic opioid blockade.

AB - Rats were implanted for 10 days with a slow-release naltrexone pellet and then the pellet was removed. Sham-control animals were treated similarly, except no pellet was implanted. One day after pellet removal or sham treatment, animals were assessed for morphine-induced conditioned place preference (CPP) or locomotor activity. CPP was evident in sham animals following two conditioning trials using 5 mg/kg subcutaneous morphine (Experiment 1) and following one conditioning trial using 8 mg/kg intravenous morphine (Experiment 2). Animals conditioned while implanted with a naltrexone pellet showed no morphine-induced CPP. More important, one day after pellet removal, naltrexone-pretreated animals given one conditioning trial with 5 mg/kg intravenous morphine displayed a greater preference for morphine-associated cues relative to sham animals given morphine (Experiment 3 and 4). This single IV morphine dose was insufficient to produce CPP in sham animals, suggesting that naltrexone-induced supersensitization may only be evident at a morphine dose below the reinforcing threshold in control animals. Further, chronic naltrexone potentiated the locomotor-activating effect of 2 mg/kg subcutaneous morphine but not of either 1 or 5 mg/kg morphine (Experiment 5). Behavioral supersensitization assessed by morphine-induced locomotor activation was transient, as it was evident one day, but not either three or 10 days following pellet removal (Experiment 6). These results confirm the functional significance of opiate receptor up-regulation following chronic opioid blockade.

KW - Conditioned place preference

KW - Locomotor activity

KW - Morphine

KW - Naltrexone

KW - Opiate receptor

KW - Receptor up-regulation

UR - http://www.scopus.com/inward/record.url?scp=0023635814&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023635814&partnerID=8YFLogxK

U2 - 10.1016/0091-3057(87)90224-3

DO - 10.1016/0091-3057(87)90224-3

M3 - Article

C2 - 2825222

AN - SCOPUS:0023635814

VL - 28

SP - 267

EP - 273

JO - Pharmacology Biochemistry and Behavior

JF - Pharmacology Biochemistry and Behavior

SN - 0091-3057

IS - 2

ER -