Tolerance to μ-opioid receptor agonists but not cross-tolerance to γ- aminobutyric acid(B) receptor agonists in arcuate A12 dopamine neurons with chronic morphine treatment

Edward J. Wagner, Ge Zhang, Andre H. Lagrange, Oline Ronnekleiv, Martin Kelly

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

The present study examined the potential for cross-tolerance development between μ-opioid and γ-aminobutyric acid(B) receptor agonists, in hypothalamic arcuate neurons, resulting from chronic morphine treatment. Intracellular recordings were made in hypothalamic slices prepared from ovariectomized female guinea pigs. The μ-opioid receptor agonist D-Ala2,N- Me-Phe4,Gly-ol5-enkephalin and the γ-aminobutyric acid(B) receptor agonist baclofen produced dose-dependent membrane hyperpolarizations of arcuate neurons. The reversal potential for both agonist-induced hyperpolarizations was near -95 mV, indicative of the activation of an underlying K+ conductance. Coadministration of maximally effective concentrations of D- Ala2,N-Me-Phe4,Gly-ol5-enkephalin and baclofen produced a response that was not additive, indicating a convergence onto a common K+ channel. In arcuate neurons, including a subset that was immunopositive for tyrosine hydroxylase, chronic morphine treatment for 4 to 7 days produced a 3.2-fold reduction in the potency, with no change in the efficacy, of D-Ala2,N-Me- Phe4,Gly-ol5-enkephalin. In contrast, it affected neither the potency nor the efficacy of baclofen. Therefore, chronic morphine exposure does not produce cross-tolerance between μ-opioid and γ-aminobutyric acid(B) receptor agonists in A12 dopamine neurons, suggesting that convergence upon a common effector is not a sufficient criterion for the development of cross- tolerance between receptor systems.

Original languageEnglish (US)
Pages (from-to)1057-1064
Number of pages8
JournalJournal of Pharmacology and Experimental Therapeutics
Volume280
Issue number2
StatePublished - 1997

Fingerprint

Aminobutyrates
compound A 12
Enkephalins
Dopaminergic Neurons
Opioid Receptors
Morphine
Baclofen
Neurons
Opioid Analgesics
GABA-B Receptors
Tyrosine 3-Monooxygenase
Guinea Pigs
Membranes

ASJC Scopus subject areas

  • Pharmacology

Cite this

@article{d31cb943f3544932a8e811bc8ee5f434,
title = "Tolerance to μ-opioid receptor agonists but not cross-tolerance to γ- aminobutyric acid(B) receptor agonists in arcuate A12 dopamine neurons with chronic morphine treatment",
abstract = "The present study examined the potential for cross-tolerance development between μ-opioid and γ-aminobutyric acid(B) receptor agonists, in hypothalamic arcuate neurons, resulting from chronic morphine treatment. Intracellular recordings were made in hypothalamic slices prepared from ovariectomized female guinea pigs. The μ-opioid receptor agonist D-Ala2,N- Me-Phe4,Gly-ol5-enkephalin and the γ-aminobutyric acid(B) receptor agonist baclofen produced dose-dependent membrane hyperpolarizations of arcuate neurons. The reversal potential for both agonist-induced hyperpolarizations was near -95 mV, indicative of the activation of an underlying K+ conductance. Coadministration of maximally effective concentrations of D- Ala2,N-Me-Phe4,Gly-ol5-enkephalin and baclofen produced a response that was not additive, indicating a convergence onto a common K+ channel. In arcuate neurons, including a subset that was immunopositive for tyrosine hydroxylase, chronic morphine treatment for 4 to 7 days produced a 3.2-fold reduction in the potency, with no change in the efficacy, of D-Ala2,N-Me- Phe4,Gly-ol5-enkephalin. In contrast, it affected neither the potency nor the efficacy of baclofen. Therefore, chronic morphine exposure does not produce cross-tolerance between μ-opioid and γ-aminobutyric acid(B) receptor agonists in A12 dopamine neurons, suggesting that convergence upon a common effector is not a sufficient criterion for the development of cross- tolerance between receptor systems.",
author = "Wagner, {Edward J.} and Ge Zhang and Lagrange, {Andre H.} and Oline Ronnekleiv and Martin Kelly",
year = "1997",
language = "English (US)",
volume = "280",
pages = "1057--1064",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Tolerance to μ-opioid receptor agonists but not cross-tolerance to γ- aminobutyric acid(B) receptor agonists in arcuate A12 dopamine neurons with chronic morphine treatment

AU - Wagner, Edward J.

AU - Zhang, Ge

AU - Lagrange, Andre H.

AU - Ronnekleiv, Oline

AU - Kelly, Martin

PY - 1997

Y1 - 1997

N2 - The present study examined the potential for cross-tolerance development between μ-opioid and γ-aminobutyric acid(B) receptor agonists, in hypothalamic arcuate neurons, resulting from chronic morphine treatment. Intracellular recordings were made in hypothalamic slices prepared from ovariectomized female guinea pigs. The μ-opioid receptor agonist D-Ala2,N- Me-Phe4,Gly-ol5-enkephalin and the γ-aminobutyric acid(B) receptor agonist baclofen produced dose-dependent membrane hyperpolarizations of arcuate neurons. The reversal potential for both agonist-induced hyperpolarizations was near -95 mV, indicative of the activation of an underlying K+ conductance. Coadministration of maximally effective concentrations of D- Ala2,N-Me-Phe4,Gly-ol5-enkephalin and baclofen produced a response that was not additive, indicating a convergence onto a common K+ channel. In arcuate neurons, including a subset that was immunopositive for tyrosine hydroxylase, chronic morphine treatment for 4 to 7 days produced a 3.2-fold reduction in the potency, with no change in the efficacy, of D-Ala2,N-Me- Phe4,Gly-ol5-enkephalin. In contrast, it affected neither the potency nor the efficacy of baclofen. Therefore, chronic morphine exposure does not produce cross-tolerance between μ-opioid and γ-aminobutyric acid(B) receptor agonists in A12 dopamine neurons, suggesting that convergence upon a common effector is not a sufficient criterion for the development of cross- tolerance between receptor systems.

AB - The present study examined the potential for cross-tolerance development between μ-opioid and γ-aminobutyric acid(B) receptor agonists, in hypothalamic arcuate neurons, resulting from chronic morphine treatment. Intracellular recordings were made in hypothalamic slices prepared from ovariectomized female guinea pigs. The μ-opioid receptor agonist D-Ala2,N- Me-Phe4,Gly-ol5-enkephalin and the γ-aminobutyric acid(B) receptor agonist baclofen produced dose-dependent membrane hyperpolarizations of arcuate neurons. The reversal potential for both agonist-induced hyperpolarizations was near -95 mV, indicative of the activation of an underlying K+ conductance. Coadministration of maximally effective concentrations of D- Ala2,N-Me-Phe4,Gly-ol5-enkephalin and baclofen produced a response that was not additive, indicating a convergence onto a common K+ channel. In arcuate neurons, including a subset that was immunopositive for tyrosine hydroxylase, chronic morphine treatment for 4 to 7 days produced a 3.2-fold reduction in the potency, with no change in the efficacy, of D-Ala2,N-Me- Phe4,Gly-ol5-enkephalin. In contrast, it affected neither the potency nor the efficacy of baclofen. Therefore, chronic morphine exposure does not produce cross-tolerance between μ-opioid and γ-aminobutyric acid(B) receptor agonists in A12 dopamine neurons, suggesting that convergence upon a common effector is not a sufficient criterion for the development of cross- tolerance between receptor systems.

UR - http://www.scopus.com/inward/record.url?scp=0030942497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0030942497&partnerID=8YFLogxK

M3 - Article

VL - 280

SP - 1057

EP - 1064

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -