[Pharmacology of central noradrenergic receptors (author's transl)]

The pharmacological characteristics of adrenergic receptors in the central nervous system (CNS) can be studied using micro-iontophoretic electrophysiological approaches and binding of radiolabeled specific adrenergic receptors ligands. These approaches allowed the identification of different sub-classes of adrenergic receptors (alpha 1, alpha 2; beta 1, beta 2) in the CNS. Some of these receptors have a noradrenergic transmission dependent regulation. At the level of cerebral cortex, regulation mechanisms were particularly well studied. Interruption of noradrenergic transmission induces an hypersensitivity of alpha and beta adrenergic receptors. The hypersensitivity is linked to an increase of receptor density, and this has been shown for alpha 1, alpha 2 and beta 1 adrenergic receptors. After repeated injections of antidepressant drugs an hyposensitivity of beta receptors was observed. More precisely these treatments induced a reduction of beta 1 binding sites, without modification of beta 2 binding sites. On the other hand, the alpha 2 binding sites were increased. These regulation processes of alpha 2 receptors appear earlier than those of beta receptors, and this phenomenon could contribute to the late appearance of beta receptors hyposensitivity. In favor of this hypothesis, the reduction of beta binding sites is induced more rapidly after coadministration of alpha 2 receptor antagonist (such as yohimbine) and antidepressant drugs. The regulation mechanisms of these different types of adrenergic receptors could contribute to the delayed action of antidepressant drugs.