Development of tolerance to benzodiazepines. I. Changes in the systems of central nervous system neurotransmitters during long-term administration of nitrazepam.

A purpose of the study was determination of the relationships between the brain levels of neuro-mediators: noradrenaline (NA), dopamine (DA), 5-hydroxytryptamine (5-HT) and gamma-aminobutyric acid (GABA) and the development of tolerance to the sedative and anticonvulsive action of Nitrazepam. It was found that during tolerance development the GABA level increased in the cerebral tissue and changes appeared in the activity state of the serotoninergic system.