AN ACUTE EFFECT OF TRIAZOLAM ON MUSCARINIC CHOLINERGIC RECEPTOR-BINDING IN THE HUMAN BRAIN MEASURED BY POSITRON EMISSION TOMOGRAPHY

An acute effect of triazolam, a potent benzodiazepine agonist, on chol inergic receptor binding in the human brain was measured by PET (posit ron emission tomography) using [C-11]N-methyl-4-piperidylbenziIate ([C -11]NMPB), a potent muscarinic cholinergic receptor antagonist. Two PE T scans were performed in each subject: (1) control scan; (2) after or al administration of 0.5 mg triazolam or placebo. The previously discu ssed amnestic effect of triazolam was measured by immediate and delaye d recall of meaningful and meaningless syllables. A compartment model employing the radioactivity in the cerebellum as an input function was used for the quantification of receptor binding. The binding paramete r, k(3), was decreased after triazolam administration in all measured regions, whereas no change was observed after placebo treatment. The r eduction compared to the control study varied from 8.6+/-3.7% in the t emporal cortex to 16.3+/-6.3% in the thalamus. Triazolam administratio n impaired both immediate and delayed recall of syllables, whereas pla cebo administration had no effects. Benzodiazepine agonists are report ed to decrease the cortical acetylcholine release. The decrease of ace tylcholine release in the synaptic cleft might be the explanation for the decreased binding of [C-11]NMPB.