Pentobarbital-enhanced [3H]flunitrazepam binding throughout the rat brain

An autoradiographic study

B. X. Carlson, A. M. Mans, R. A. Hawkins, Helen Baghdoyan

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

The γ-aminobutyric acid(A)/benzodiazepine receptor contains distinct ligand binding sites for hypnotic barbiturates and benzodiazepines. It is thought that barbiturate-induced sedation is produced, in part, by enhancing agonist binding to this receptor. The present study tested the hypothesis that pentobarbital would enhance benzodiazepine binding in a site-specific manner across the rat brain. In vitro receptor autoradiography was used to localize and quantitatively map [3H]flunitrazepam ([3H]FLU) binding in the absence and presence of pentobarbital in 133 brain areas. Each area demonstrated a statistically significant increase in [3H]FLU binding in the presence of in vitro pentobarbital (P ≤ .05). Hindbrain nuclei dominated the top 20% of brain areas demonstrating the greatest pentobarbital-induced increases in [3H]FLU binding. The greatest mean percent increase in [3H]FLU binding occurred in the medulla, including areas known to be important for cardiovascular control, breathing, motor tone and regulating levels of arousal. These findings show that differential enhancement of benzodiazepine binding in the presence of pentobarbital occurred in brain areas controlling physiological functions known to be impaired by systemically administered pentobarbital.

Original languageEnglish (US)
Pages (from-to)1401-1414
Number of pages14
JournalJournal of Pharmacology and Experimental Therapeutics
Volume263
Issue number3
StatePublished - 1992
Externally publishedYes

Fingerprint

Flunitrazepam
Pentobarbital
Brain
Benzodiazepines
Aminobutyrates
Rhombencephalon
Barbiturates
GABA-A Receptors
Arousal
Autoradiography
Hypnotics and Sedatives
Respiration
Binding Sites
Ligands

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Pentobarbital-enhanced [3H]flunitrazepam binding throughout the rat brain : An autoradiographic study. / Carlson, B. X.; Mans, A. M.; Hawkins, R. A.; Baghdoyan, Helen.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 263, No. 3, 1992, p. 1401-1414.

Research output: Contribution to journalArticle

@article{102173784ec34c9789082eac03bcc915,
title = "Pentobarbital-enhanced [3H]flunitrazepam binding throughout the rat brain: An autoradiographic study",
abstract = "The γ-aminobutyric acid(A)/benzodiazepine receptor contains distinct ligand binding sites for hypnotic barbiturates and benzodiazepines. It is thought that barbiturate-induced sedation is produced, in part, by enhancing agonist binding to this receptor. The present study tested the hypothesis that pentobarbital would enhance benzodiazepine binding in a site-specific manner across the rat brain. In vitro receptor autoradiography was used to localize and quantitatively map [3H]flunitrazepam ([3H]FLU) binding in the absence and presence of pentobarbital in 133 brain areas. Each area demonstrated a statistically significant increase in [3H]FLU binding in the presence of in vitro pentobarbital (P ≤ .05). Hindbrain nuclei dominated the top 20{\%} of brain areas demonstrating the greatest pentobarbital-induced increases in [3H]FLU binding. The greatest mean percent increase in [3H]FLU binding occurred in the medulla, including areas known to be important for cardiovascular control, breathing, motor tone and regulating levels of arousal. These findings show that differential enhancement of benzodiazepine binding in the presence of pentobarbital occurred in brain areas controlling physiological functions known to be impaired by systemically administered pentobarbital.",
author = "Carlson, {B. X.} and Mans, {A. M.} and Hawkins, {R. A.} and Helen Baghdoyan",
year = "1992",
language = "English (US)",
volume = "263",
pages = "1401--1414",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - Pentobarbital-enhanced [3H]flunitrazepam binding throughout the rat brain

T2 - An autoradiographic study

AU - Carlson, B. X.

AU - Mans, A. M.

AU - Hawkins, R. A.

AU - Baghdoyan, Helen

PY - 1992

Y1 - 1992

N2 - The γ-aminobutyric acid(A)/benzodiazepine receptor contains distinct ligand binding sites for hypnotic barbiturates and benzodiazepines. It is thought that barbiturate-induced sedation is produced, in part, by enhancing agonist binding to this receptor. The present study tested the hypothesis that pentobarbital would enhance benzodiazepine binding in a site-specific manner across the rat brain. In vitro receptor autoradiography was used to localize and quantitatively map [3H]flunitrazepam ([3H]FLU) binding in the absence and presence of pentobarbital in 133 brain areas. Each area demonstrated a statistically significant increase in [3H]FLU binding in the presence of in vitro pentobarbital (P ≤ .05). Hindbrain nuclei dominated the top 20% of brain areas demonstrating the greatest pentobarbital-induced increases in [3H]FLU binding. The greatest mean percent increase in [3H]FLU binding occurred in the medulla, including areas known to be important for cardiovascular control, breathing, motor tone and regulating levels of arousal. These findings show that differential enhancement of benzodiazepine binding in the presence of pentobarbital occurred in brain areas controlling physiological functions known to be impaired by systemically administered pentobarbital.

AB - The γ-aminobutyric acid(A)/benzodiazepine receptor contains distinct ligand binding sites for hypnotic barbiturates and benzodiazepines. It is thought that barbiturate-induced sedation is produced, in part, by enhancing agonist binding to this receptor. The present study tested the hypothesis that pentobarbital would enhance benzodiazepine binding in a site-specific manner across the rat brain. In vitro receptor autoradiography was used to localize and quantitatively map [3H]flunitrazepam ([3H]FLU) binding in the absence and presence of pentobarbital in 133 brain areas. Each area demonstrated a statistically significant increase in [3H]FLU binding in the presence of in vitro pentobarbital (P ≤ .05). Hindbrain nuclei dominated the top 20% of brain areas demonstrating the greatest pentobarbital-induced increases in [3H]FLU binding. The greatest mean percent increase in [3H]FLU binding occurred in the medulla, including areas known to be important for cardiovascular control, breathing, motor tone and regulating levels of arousal. These findings show that differential enhancement of benzodiazepine binding in the presence of pentobarbital occurred in brain areas controlling physiological functions known to be impaired by systemically administered pentobarbital.

UR - http://www.scopus.com/inward/record.url?scp=0027007713&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027007713&partnerID=8YFLogxK

M3 - Article

VL - 263

SP - 1401

EP - 1414

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -