M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse

Christopher L. Douglas, Helen Baghdoyan, Ralph Lydic

Research output: Contribution to journalArticle

60 Citations (Scopus)

Abstract

Muscarinic autoreceptors modulate cholinergic neurotransmission in animals ranging from insects to humans. No previous studies have characterized autoreceptor modulation of acetylcholine (ACh) release in prefrontal cortex of intact mouse. Data obtained from experiments in 45 mice considered ACh as a phenotype and tested the hypothesis that pharmacologically defined M2 receptors modulate ACh release in prefrontal cortex of C57BL/6J mouse. In vivo microdialysis quantified ACh release during delivery of Ringer's (control) or Ringer's containing muscarinic receptor antagonists. The lowest concentration of each antagonist [scopolamine, pirenzepine, or 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzodiazepine-one (AF-DX116)] that significantly increased ACh release was determined and defined as the minimum ACh-releasing concentration. Dialysis delivery of scopolamine caused a concentration-dependent increase in ACh release, consistent with the existence of muscarinic auto receptors. The order of potency for causing increased ACh release was scopolamine = AF-DX116 > pirenzepine. Administration of pertussis toxin into prefrontal cortex blocked the AF-DX116-induced increase in ACh release. These findings support the conclusion that M2 receptors modulate ACh release in C57BL/6J mouse prefrontal cortex. Nearly every human gene has a mouse homolog and the appeal of mouse models is reinforced by the identification of mouse genes causing phenotypic deviants. The present data encourage comparative phenotyping of cortical ACh release in additional mouse strains.

Original languageEnglish (US)
Pages (from-to)960-966
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume299
Issue number3
StatePublished - Dec 12 2001

Fingerprint

Autoreceptors
Prefrontal Cortex
Inbred C57BL Mouse
Cholinergic Agents
Acetylcholine
Scopolamine Hydrobromide
Pirenzepine
Cholinergic Receptors
Muscarinic Receptors
Muscarinic Antagonists
Pertussis Toxin
Microdialysis
Synaptic Transmission
Genes
Insects
Dialysis
Phenotype

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Pharmacology

Cite this

M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse. / Douglas, Christopher L.; Baghdoyan, Helen; Lydic, Ralph.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 299, No. 3, 12.12.2001, p. 960-966.

Research output: Contribution to journalArticle

@article{8e21d93d5db9447ebc22a8cb1da40787,
title = "M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse",
abstract = "Muscarinic autoreceptors modulate cholinergic neurotransmission in animals ranging from insects to humans. No previous studies have characterized autoreceptor modulation of acetylcholine (ACh) release in prefrontal cortex of intact mouse. Data obtained from experiments in 45 mice considered ACh as a phenotype and tested the hypothesis that pharmacologically defined M2 receptors modulate ACh release in prefrontal cortex of C57BL/6J mouse. In vivo microdialysis quantified ACh release during delivery of Ringer's (control) or Ringer's containing muscarinic receptor antagonists. The lowest concentration of each antagonist [scopolamine, pirenzepine, or 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzodiazepine-one (AF-DX116)] that significantly increased ACh release was determined and defined as the minimum ACh-releasing concentration. Dialysis delivery of scopolamine caused a concentration-dependent increase in ACh release, consistent with the existence of muscarinic auto receptors. The order of potency for causing increased ACh release was scopolamine = AF-DX116 > pirenzepine. Administration of pertussis toxin into prefrontal cortex blocked the AF-DX116-induced increase in ACh release. These findings support the conclusion that M2 receptors modulate ACh release in C57BL/6J mouse prefrontal cortex. Nearly every human gene has a mouse homolog and the appeal of mouse models is reinforced by the identification of mouse genes causing phenotypic deviants. The present data encourage comparative phenotyping of cortical ACh release in additional mouse strains.",
author = "Douglas, {Christopher L.} and Helen Baghdoyan and Ralph Lydic",
year = "2001",
month = "12",
day = "12",
language = "English (US)",
volume = "299",
pages = "960--966",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "3",

}

TY - JOUR

T1 - M2 muscarinic autoreceptors modulate acetylcholine release in prefrontal cortex of C57BL/6J mouse

AU - Douglas, Christopher L.

AU - Baghdoyan, Helen

AU - Lydic, Ralph

PY - 2001/12/12

Y1 - 2001/12/12

N2 - Muscarinic autoreceptors modulate cholinergic neurotransmission in animals ranging from insects to humans. No previous studies have characterized autoreceptor modulation of acetylcholine (ACh) release in prefrontal cortex of intact mouse. Data obtained from experiments in 45 mice considered ACh as a phenotype and tested the hypothesis that pharmacologically defined M2 receptors modulate ACh release in prefrontal cortex of C57BL/6J mouse. In vivo microdialysis quantified ACh release during delivery of Ringer's (control) or Ringer's containing muscarinic receptor antagonists. The lowest concentration of each antagonist [scopolamine, pirenzepine, or 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzodiazepine-one (AF-DX116)] that significantly increased ACh release was determined and defined as the minimum ACh-releasing concentration. Dialysis delivery of scopolamine caused a concentration-dependent increase in ACh release, consistent with the existence of muscarinic auto receptors. The order of potency for causing increased ACh release was scopolamine = AF-DX116 > pirenzepine. Administration of pertussis toxin into prefrontal cortex blocked the AF-DX116-induced increase in ACh release. These findings support the conclusion that M2 receptors modulate ACh release in C57BL/6J mouse prefrontal cortex. Nearly every human gene has a mouse homolog and the appeal of mouse models is reinforced by the identification of mouse genes causing phenotypic deviants. The present data encourage comparative phenotyping of cortical ACh release in additional mouse strains.

AB - Muscarinic autoreceptors modulate cholinergic neurotransmission in animals ranging from insects to humans. No previous studies have characterized autoreceptor modulation of acetylcholine (ACh) release in prefrontal cortex of intact mouse. Data obtained from experiments in 45 mice considered ACh as a phenotype and tested the hypothesis that pharmacologically defined M2 receptors modulate ACh release in prefrontal cortex of C57BL/6J mouse. In vivo microdialysis quantified ACh release during delivery of Ringer's (control) or Ringer's containing muscarinic receptor antagonists. The lowest concentration of each antagonist [scopolamine, pirenzepine, or 11-2[(-[(diethylamino)methyl]-1-piperidinyl)-acetyl]-5,11-dihydro-6H-pyrido (2,3-b)(1,4)-benzodiazepine-one (AF-DX116)] that significantly increased ACh release was determined and defined as the minimum ACh-releasing concentration. Dialysis delivery of scopolamine caused a concentration-dependent increase in ACh release, consistent with the existence of muscarinic auto receptors. The order of potency for causing increased ACh release was scopolamine = AF-DX116 > pirenzepine. Administration of pertussis toxin into prefrontal cortex blocked the AF-DX116-induced increase in ACh release. These findings support the conclusion that M2 receptors modulate ACh release in C57BL/6J mouse prefrontal cortex. Nearly every human gene has a mouse homolog and the appeal of mouse models is reinforced by the identification of mouse genes causing phenotypic deviants. The present data encourage comparative phenotyping of cortical ACh release in additional mouse strains.

UR - http://www.scopus.com/inward/record.url?scp=0035196924&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035196924&partnerID=8YFLogxK

M3 - Article

VL - 299

SP - 960

EP - 966

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 3

ER -