Triazolam-induced modulation of muscarinic acetylcholine receptor in living brain slices as revealed by a new positron-based imaging technique

The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB...

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Bibliographic Details
Published in:Journal of Neural Transmission 1998-01, Vol.105 (10-12), p.1117-1127
Main Authors: MURATA, T, MATSUMURA, K, SIHVER, S, ONOE, H, BERGSTRÖM, M, SIHVER, W, YONEKURA, Y, LANGSTRÖM, B, WATANABE, Y
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Brain - drug effects
Brain - metabolism
Flumazenil - pharmacology
GABA Agonists - pharmacology
Gabaergic and benzodiazepinic system
In Vitro Techniques
Male
Medical sciences
Muscimol - pharmacology
Neuropharmacology
Neurotransmitters. Neurotransmission. Receptors
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Receptors, Muscarinic - metabolism
Tomography, Emission-Computed - methods
Triazolam - pharmacology
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Summary:The effect of triazolam, a potent benzodiazepine (BZ) agonist, on muscarinic acetylcholinergic receptor (mAChR) binding was investigated in living brain slices by use of a novel positron-based imaging technique. Fresh rat brain slices were incubated with [11C]N-methyl-4-piperidylbenzilate ([11C]NMPB), a mAChR antagonist, in oxygenated Krebs-Ringer solution at 37 degrees C. During incubation, time-resolved imaging of [11C]NMPB binding in the slices was constructed on the storage phosphor screens. Addition of triazolam (1 microM) plus muscimol (30 microM), a GABA(A) receptor agonist, to the incubation mixture decreased the specific binding of [11C]NMPB. Ro15-1788, a BZ receptor antagonist, prevented this effect, indicating that the effect was exerted through the GABA(A)/BZ receptor complex. These results demonstrated that stimulation of the GABA(A)/BZ receptor lowers the affinity of the mAChR for its ligand, which may underlie the BZ-induced amnesia, a serious clinical side effect of BZ. No such effect in the P2-fraction instead implies that the integrity of the neuronal cells and/or their environment is prerequisite for the modulation of mAChR by GABA(A)/BZ stimulation.
ISSN:0300-9564
1435-1463
DOI:10.1007/s007020050116