Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice

Laurence L Miller, Mitchell J. Picker, Karl T. Schmidt, Linda A. Dykstra

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Rationale Pharmacological manipulations of the type 1 cannabinoid receptor (CB1) suggest a role for CB1 in morphine-induced antinociception, but studies utilizing CB1 knockout (KO) mice do not support this conclusion. Since studies using CB1 KO mice to study morphine's antinociceptive effects have only examined thermal nociception, this study examines these interactions in models that employ a chemical stimulus. Objectives To determine whether the findings obtained with thermal pain models extend to other models, the effects of morphine on acetic acid-induced writhing were examined in CB1 KO and wildtype (WT) mice. Behaviors that decrease in response to acid injection, feeding and wheel running, were also examined, and investigations were carried out in the thermal hotplate assay. The CB1 antagonist SR141716A was also examined in these assays. Results Morphine completely blocked acid-induced writhing (1.0-10.0 mg/kg) and increased response latencies in the hotplate (10.0-32.0 mg/kg) in both genotypes. Morphine (3.2 mg/kg) significantly attenuated the suppression of wheel running but did not completely prevent this effect in either genotype. Morphine did not alter pain-suppressed feeding. In each of these assays, morphine's effects were not altered in CB1 KO mice compared with WT mice; however, SR141716A attenuated morphine's effects in C57BL/6 mice. Conclusions The effects of morphine do not differ in CB1 KO and WT mice in preclinical pain models using thermal and chemical stimuli. Since SR141716A did attenuate the effects of morphine, it is possible that CB1 KO mice undergo developmental changes that mask the role of CB1 receptors in morphine's antinociceptive effects.

Original languageEnglish (US)
Pages (from-to)455-465
Number of pages11
JournalPsychopharmacology
Volume215
Issue number3
DOIs
StatePublished - Jun 1 2011
Externally publishedYes

Fingerprint

Knockout Mice
Morphine
rimonabant
Pain
Hot Temperature
Cannabinoid Receptor CB1
Running
Genotype
Acids
Nociception
Masks
Inbred C57BL Mouse
Acetic Acid
Reaction Time
Pharmacology
Injections

Keywords

  • Antagonist
  • Antinociception
  • CB1
  • Cannabinoid
  • Knockout
  • Morphine
  • Opioid
  • Pain

ASJC Scopus subject areas

  • Pharmacology

Cite this

Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice. / Miller, Laurence L; Picker, Mitchell J.; Schmidt, Karl T.; Dykstra, Linda A.

In: Psychopharmacology, Vol. 215, No. 3, 01.06.2011, p. 455-465.

Research output: Contribution to journalArticle

Miller, Laurence L ; Picker, Mitchell J. ; Schmidt, Karl T. ; Dykstra, Linda A. / Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice. In: Psychopharmacology. 2011 ; Vol. 215, No. 3. pp. 455-465.
@article{ce925c725ef5410e8f03592000d220af,
title = "Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice",
abstract = "Rationale Pharmacological manipulations of the type 1 cannabinoid receptor (CB1) suggest a role for CB1 in morphine-induced antinociception, but studies utilizing CB1 knockout (KO) mice do not support this conclusion. Since studies using CB1 KO mice to study morphine's antinociceptive effects have only examined thermal nociception, this study examines these interactions in models that employ a chemical stimulus. Objectives To determine whether the findings obtained with thermal pain models extend to other models, the effects of morphine on acetic acid-induced writhing were examined in CB1 KO and wildtype (WT) mice. Behaviors that decrease in response to acid injection, feeding and wheel running, were also examined, and investigations were carried out in the thermal hotplate assay. The CB1 antagonist SR141716A was also examined in these assays. Results Morphine completely blocked acid-induced writhing (1.0-10.0 mg/kg) and increased response latencies in the hotplate (10.0-32.0 mg/kg) in both genotypes. Morphine (3.2 mg/kg) significantly attenuated the suppression of wheel running but did not completely prevent this effect in either genotype. Morphine did not alter pain-suppressed feeding. In each of these assays, morphine's effects were not altered in CB1 KO mice compared with WT mice; however, SR141716A attenuated morphine's effects in C57BL/6 mice. Conclusions The effects of morphine do not differ in CB1 KO and WT mice in preclinical pain models using thermal and chemical stimuli. Since SR141716A did attenuate the effects of morphine, it is possible that CB1 KO mice undergo developmental changes that mask the role of CB1 receptors in morphine's antinociceptive effects.",
keywords = "Antagonist, Antinociception, CB1, Cannabinoid, Knockout, Morphine, Opioid, Pain",
author = "Miller, {Laurence L} and Picker, {Mitchell J.} and Schmidt, {Karl T.} and Dykstra, {Linda A.}",
year = "2011",
month = "6",
day = "1",
doi = "10.1007/s00213-011-2232-5",
language = "English (US)",
volume = "215",
pages = "455--465",
journal = "Psychopharmacology",
issn = "0033-3158",
publisher = "Springer Verlag",
number = "3",

}

TY - JOUR

T1 - Effects of morphine on pain-elicited and pain-suppressed behavior in CB1 knockout and wildtype mice

AU - Miller, Laurence L

AU - Picker, Mitchell J.

AU - Schmidt, Karl T.

AU - Dykstra, Linda A.

PY - 2011/6/1

Y1 - 2011/6/1

N2 - Rationale Pharmacological manipulations of the type 1 cannabinoid receptor (CB1) suggest a role for CB1 in morphine-induced antinociception, but studies utilizing CB1 knockout (KO) mice do not support this conclusion. Since studies using CB1 KO mice to study morphine's antinociceptive effects have only examined thermal nociception, this study examines these interactions in models that employ a chemical stimulus. Objectives To determine whether the findings obtained with thermal pain models extend to other models, the effects of morphine on acetic acid-induced writhing were examined in CB1 KO and wildtype (WT) mice. Behaviors that decrease in response to acid injection, feeding and wheel running, were also examined, and investigations were carried out in the thermal hotplate assay. The CB1 antagonist SR141716A was also examined in these assays. Results Morphine completely blocked acid-induced writhing (1.0-10.0 mg/kg) and increased response latencies in the hotplate (10.0-32.0 mg/kg) in both genotypes. Morphine (3.2 mg/kg) significantly attenuated the suppression of wheel running but did not completely prevent this effect in either genotype. Morphine did not alter pain-suppressed feeding. In each of these assays, morphine's effects were not altered in CB1 KO mice compared with WT mice; however, SR141716A attenuated morphine's effects in C57BL/6 mice. Conclusions The effects of morphine do not differ in CB1 KO and WT mice in preclinical pain models using thermal and chemical stimuli. Since SR141716A did attenuate the effects of morphine, it is possible that CB1 KO mice undergo developmental changes that mask the role of CB1 receptors in morphine's antinociceptive effects.

AB - Rationale Pharmacological manipulations of the type 1 cannabinoid receptor (CB1) suggest a role for CB1 in morphine-induced antinociception, but studies utilizing CB1 knockout (KO) mice do not support this conclusion. Since studies using CB1 KO mice to study morphine's antinociceptive effects have only examined thermal nociception, this study examines these interactions in models that employ a chemical stimulus. Objectives To determine whether the findings obtained with thermal pain models extend to other models, the effects of morphine on acetic acid-induced writhing were examined in CB1 KO and wildtype (WT) mice. Behaviors that decrease in response to acid injection, feeding and wheel running, were also examined, and investigations were carried out in the thermal hotplate assay. The CB1 antagonist SR141716A was also examined in these assays. Results Morphine completely blocked acid-induced writhing (1.0-10.0 mg/kg) and increased response latencies in the hotplate (10.0-32.0 mg/kg) in both genotypes. Morphine (3.2 mg/kg) significantly attenuated the suppression of wheel running but did not completely prevent this effect in either genotype. Morphine did not alter pain-suppressed feeding. In each of these assays, morphine's effects were not altered in CB1 KO mice compared with WT mice; however, SR141716A attenuated morphine's effects in C57BL/6 mice. Conclusions The effects of morphine do not differ in CB1 KO and WT mice in preclinical pain models using thermal and chemical stimuli. Since SR141716A did attenuate the effects of morphine, it is possible that CB1 KO mice undergo developmental changes that mask the role of CB1 receptors in morphine's antinociceptive effects.

KW - Antagonist

KW - Antinociception

KW - CB1

KW - Cannabinoid

KW - Knockout

KW - Morphine

KW - Opioid

KW - Pain

UR - http://www.scopus.com/inward/record.url?scp=80052333893&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052333893&partnerID=8YFLogxK

U2 - 10.1007/s00213-011-2232-5

DO - 10.1007/s00213-011-2232-5

M3 - Article

C2 - 21373789

AN - SCOPUS:80052333893

VL - 215

SP - 455

EP - 465

JO - Psychopharmacology

JF - Psychopharmacology

SN - 0033-3158

IS - 3

ER -