Pharmacology and Distribution of Norepinephrine Transporters in the Human Locus Coeruleus and Raphe Nuclei

Abstract

The norepinephrine transporter (NET ) is a site of action for tricyclic antidepressant drugs and for drugs of abuse such as amphetamine and cocaine. In this study, the binding of [ 3 H]nisoxetine to NETs in the noradrenergic cell group, the locus coeruleus, and the serotonergic cell groups, the dorsal raphe nuclei, was measured autoradiographically in postmortem human brain. 3 H]nisoxetine binding to NETs in monoaminergic nuclei was assessed by measuring the inhibition of its binding by desipramine, imipramine, or citalopram. The order of affinities of these drugs was identical in the locus coeruleus and dorsal and median raphe and was characteristic of binding to NETs (desipramine Ͼ imipramine Ͼ citalopram). Thus, high levels of NETs and an uneven distribution of NETs occur in the locus coeruleus as well as in the dorsal raphe nuclei of the human.

Anticipatory postural adjustments stabilise the whole upper-limb prior to a gentle index finger tap

“…consistent NET component localized on terminal projections arising from more caudal noradrenergic cell groups [21]. In PD, reduced dopamine release from nigro-striatal projections results in loss and adaptive down-regulation of DAT binding sites in the striatal region [22].…”

Elevated Concentrations of CRF in the Locus Coeruleus of Depressed Subjects

“…A toxicology screen on blood, bile, and urine from all of the subjects was performed by the Cuyahoga County Coroner's Office as described previously Ordway et al, 1997). Qualitative and quantitative assays were used to detect the following compounds or classes of compounds: ethanol, barbiturates, benzodiazepines, sympathomimetic drugs, and many antidepressant and antipsychotic drugs and their metabolites.…”

Control of 5-Hydroxytryptamine Release in the Dorsal Raphe Nucleus by the Noradrenergic System in Rat Brain. Role of α-Adrenoceptors

“…Neurochemical studies have revealed the presence of noradrenaline and NA uptake sites in the DR (Saavedra et al, 1976;Tejani-Butt, 1992;Ordway et al, 1997;Strazielle et al, 1999). Autoradiographic, immunohistochemical, and in situ hybridization studies show an abundance of a 1 -adrenoceptors in the DR, whereas the presence of a 2 -adrenoceptors is not accompanied by their encoding mRNA (Unnerstall et al, 1984;Pieribone et al, 1994;Nicholas et al, 1996;Rosin et al, 1996;Talley et al, 1996;Day et al, 1997;Winzer-Serhan et al, 1997a, b).…”