Brain neurotransmitter changes in human narcolepsy

We measured the concentrations of the three major monoamine neurotransmitters nor adrenaline, dopamine, and serotonin, their metabolites, and receptor binding sites in autopsied brain of three patients with narcolepsy. As compared with the controls, concentrations of the noradrenaline and serotonin metabolites MHPG and 5-HIAA, respectively, were markedly elevated in cerebral cortical subdivisions of the narcolepsy patients together with a trend for above-normal neurotransmitter/metabolite “turnover” ratio. A moderately reduced number of 1 -adrenoceptors, as judged by the reduced levels of 3 H-prazosin binding, was observed in cerebral cortex of two of the three patients with narcolepsy. Mean striatal levels of dopamine and its metabolite hoinovanillic acid were normal, whereas the concentration of dopamine9s second metabolite, dihydroxyphenylacetic acid, was markedly reduced by 50% or greater. This was accompanied by a marked increase (+125%) in mean 3 H-spiperone binding to the D 2 dopamine receptor in both caudate and putarnen; in contrast, the levels of 3 H-SCH 23390 binding to the striatal D 1 dopamine receptor were in the normal range. Our data provide evidence for altered brain monoaminergic neurotransmitter function in human narcolepsy.