Autoradiographic studies of post-mortem human narcoleptic brain

Although the pathological basis for narcolepsy is unknown, studies of human and canine narcolepsy have suggested that monoamine and cholinergic metabolism may be altered. We used quantitative autoradiography to assess binding of dopaminergic, noradrenergic, and cholinergic ligands to basal ganglia and amygdala of five narcoleptic and 17 control human brains. Dopamine receptor studies revealed significant increases in D-1 and D-2 receptor binding in the caudate nucleus, as well as large but not significant increases of D-1 binding in the medial globus pallidus, and D-2 binding in the lateral globus pallidus and the lateral nucleus of the amygdala. Alpha-adrenergic receptor studies revealed a significant increase in alpha-2 receptor binding in the putamen and large but not significant increases of alpha-2 binding in the caudate nucleus, and basal and lateral nuclei of the amygdala. Alpha-1 receptor binding was decreased in several areas but the changes were not statistically significant. Studies of two narcoleptic brains revealed small but not statistically significant increases in muscarinic receptor binding in the caudate nucleus, putamen, and amygdala. Although we cannot exclude the possibility that stimulant medications used before death may be partly responsible for these findings, the results suggest that human narcolepsy is associated with upregulation of dopamine and alpha-2 adrenergic receptors in specific brain regions.