Amitriptyline: Long-term treatment elevates α-adrenergic and muscarinic receptor binding in mouse brain

The effects of long-term treatment of the tricyclic antidepressant drug, amitriptyline, on α-adrenergic, muscarinic and dopaminergic receptor binding were studied in mouse brain. No changes could be observed after 7 or 14 days of amitriptyline administration, but after 21 days a two-fold increase in α-adrenergic binding was detected in the medulla pons and in the hippocampus using [³H]WB-4101 as the binding ligand. In the same regions, a moderate increase in muscarinic receptor binding (25%) as measured by [³H]4NMPB was seen, while no change was detected in dopaminergic receptor binding measured by [³H]spiperone. Scatchard analysis reveals that the increases in receptor densities are not a result of changes in the dissociation constants of the tritiated drugs for their receptors. It is suggested that the increase in α-adrenergic as well as in muscarinic binding is a consequence of a chronic blockade of these two types of receptors by amitriptyline in vivo.