PHARMACOLOGY AND DISTRIBUTION OF NOREPINEPHRINE TRANSPORTERS IN THE HUMAN LOCUS-COERULEUS AND RAPHE NUCLEI

The norepinephrine transporter (NET) is a site of action for tricyclic antidepressant drugs and for drugs of abuse such as amphetamine and c ocaine. In this study, the binding of [H-3]nisoxetine to NETs in the n oradrenergic cell group, the locus coeruleus, and the serotonergic cel l groups, the dorsal raphe nuclei, was measured autoradiographically i n postmortem human brain. [H-3]nisoxetine binding was unevenly distrib uted along the rostral-caudal axis of the locus coeruleus and correlat ed positively with numbers of neuromelanin-containing (noradrenergic) cells along the axis of the locus coeruleus within individuals. Bindin g densities of [H-3]nisoxetine in dorsal raphe nuclei were similar to that in the locus coeruleus. [H-3]nisoxetine binding was unevenly dist ributed along the entire rostral-caudal extent of the dorsal raphe, wi th the highest binding occurring in the interfascicular and ventral nu clei. A moderate amount of [H-3]nisoxetine binding was also observed i n the median raphe nucleus. The specificity of [H-3]nisoxetine binding to NETs in monoaminergic nuclei was assessed by measuring the inhibit ion of its binding by desipramine, imipramine, or citalopram. The orde r of affinities of these drugs was identical in the locus coeruleus an d dorsal and median raphe and was characteristic of binding to NETs (d esipramine > imipramine > citalopram). Thus, high levels of NETs and a n uneven distribution of NETs occur in the locus coeruleus as well as in the dorsal raphe nuclei of the human.