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 language | English (US) |
|---|---|
| Pages (from-to) | 1057-1064 |
| Number of pages | 8 |
| Journal | Journal of Pharmacology and Experimental Therapeutics |
| Volume | 280 |
| Issue number | 2 |
| State | Published - 1997 |
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ASJC Scopus subject areas
- Pharmacology
Cite this
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. / Wagner, Edward J.; Zhang, Ge; Lagrange, Andre H.; Ronnekleiv, Oline; Kelly, Martin.
In: Journal of Pharmacology and Experimental Therapeutics, Vol. 280, No. 2, 1997, p. 1057-1064.Research output: Contribution to journal › Article
}
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.
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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 -