Role of NMDA receptors in pentobarbital tolerance/dependence

Seikwan Oh; Katsuji Hoshi; I. K. Ho

doi:10.1023/A:1022019423197

Role of NMDA receptors in pentobarbital tolerance/dependence

Seikwan Oh, Katsuji Hoshi, I. K. Ho

Department of Molecular Medicine

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Effects of continuous pentobarbital administration on binding characteristics of [³H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300μg/10μl/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [³H]MK- 801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10μ1/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [³⁵S]TBPS binding was significantly attenuated by co-infusion with MK801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.

Original language	English
Pages (from-to)	767-774
Number of pages	8
Journal	Neurochemical Research
Volume	22
Issue number	7
DOIs	https://doi.org/10.1023/A:1022019423197
State	Published - 1997

Bibliographical note

Funding Information:
The authors thank Dr. Ma for his technical assistance and Dr. Susan E. Wellman for her helpful review of the manuscript. The study was supported by a grant NIDA 04480.

Keywords

Autoradiography
MK-801
Pentobarbital
TBPS

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title = "Role of NMDA receptors in pentobarbital tolerance/dependence",

abstract = "Effects of continuous pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300μg/10μl/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [3H]MK- 801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10μ1/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.",

keywords = "Autoradiography, MK-801, Pentobarbital, TBPS",

author = "Seikwan Oh and Katsuji Hoshi and Ho, {I. K.}",

note = "Funding Information: The authors thank Dr. Ma for his technical assistance and Dr. Susan E. Wellman for her helpful review of the manuscript. The study was supported by a grant NIDA 04480.",

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doi = "10.1023/A:1022019423197",

language = "English",

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journal = "Neurochemical Research",

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T1 - Role of NMDA receptors in pentobarbital tolerance/dependence

AU - Oh, Seikwan

AU - Hoshi, Katsuji

AU - Ho, I. K.

N1 - Funding Information: The authors thank Dr. Ma for his technical assistance and Dr. Susan E. Wellman for her helpful review of the manuscript. The study was supported by a grant NIDA 04480.

PY - 1997

Y1 - 1997

N2 - Effects of continuous pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300μg/10μl/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [3H]MK- 801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10μ1/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.

AB - Effects of continuous pentobarbital administration on binding characteristics of [3H]MK-801 in the rat brain were examined by autoradiography. Animals were rendered tolerant to pentobarbital using i.c.v. infusion of pentobarbital (300μg/10μl/hr for 7 days) by osmotic minipumps and dependent by abrupt withdrawal from pentobarbital. The levels of [3H]MK- 801 binding were elevated in rats 24-hr after withdrawal from pentobarbital while there were no changes except in septum and anterior ventral nuclei in tolerant rats. For assessing the role of NMDA receptor in barbiturate action, an NMDA receptor antagonist (MK-801, 2.7 femto g/10μ1/hr) was co-infused with pentobarbital. The pentobarbital-infused group had a shorter duration of pentobarbital-induced loss of righting reflex (sleeping time) than that of the control group, and MK-801 alone did not affect the righting reflex. However, co-infusion of MK-801 blocked hyperthermia, and prolonged the onset of convulsions induced by t-butylbicyclophosphorothionate (TBPS) in pentobarbital withdrawal rats. In addition, elevated [35S]TBPS binding was significantly attenuated by co-infusion with MK801. These results suggest the involvement of NMDA receptor up-regulation in pentobarbital withdrawal and that the development of dependence can be attenuated by the treatment of subtoxic dose of MK-801.

KW - Autoradiography

KW - MK-801

KW - Pentobarbital

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JO - Neurochemical Research

JF - Neurochemical Research

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ER -

Role of NMDA receptors in pentobarbital tolerance/dependence

Abstract

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Keywords

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