The complex binding of tricyclic antidepressants to rat brain: the case of nortriptyline

[3H]Nortriptyline (NT) binding to rat brain sections was characterized using saturation and competition experiments, quantitative autoradiographic localization and monoaminergic lesions. [3H]NT binding exhibits a saturable component in the nM range (high affinity binding). Final saturation is reached only in micromolar concentrations (low affinity binding). The high affinity binding sites of [3H]NT appear in areas rich in noradrenergic and serotonergic terminals, and are decreased by 6-OHDA and 5,7-DHT lesions, to an extent depending on the brain region and the relative density of noradrenergic and serotonergic terminals there. We conclude that [3H]NT binds with high affinity to both noradrenergic and serotonergic nerve terminals, and with low affinity to other yet uncharacterized entities. This complex binding pattern is compatible with the multiplicity of biochemical, physiological and behavioral effects of NT and tricyclic antidepressants in general.