The serotonin-norepinephrine link hypothesis of affective disorders: receptor-receptor interactions in brain.

Abstract

The morphological organization of central monoamine systems has suggested a functional linkage of noradrenergic and serotonergic neurons ever since Dahlstrom and Fuxe (1964) demonstrated, by means of a sensitive fluorescence method, the neuronal localization of norepinephrine (NE) and serotonin (5HT) and mapped NE and 5HT containing cell bodies and terminals in the central nervous system. These and more recent studies show that NE and 5HT neurons form monosynaptic pathways between the lower brain stem and the cerebral cortex (Dahlstrom and Fuxe, 1964; Anden et al., 1966; Moore and Bloom, 1979; Levitt and Moore, 1978; Morrison et al., 1982; Consolazione and Cuello, 1982). With the introduction of immunohistochemical techniques, it became evident that NE and 5HT containing neurons project to the entire neuraxis and, within the cerebral cortex, to all six cortical layers, though some topographical and species differences exist (Lindvall and Bjorklund, 1984; Levitt et al., 1984). Early work also indicated a high degree of catecholamine innervation of 5HT cell bodies in the raphe nuclei (Dahlstrom and Fuxe, 1964) and the existence of a 5HT innervation of NE cell bodies in the locus coeruleus (Pickel et al., 1975). The details of the monoaminergic pathways in the central nervous system have been authoritatively reviewed (Jacobowitz, 1978; Moore and Bloom, 1979; Consolazione and Cuello, 1982). As pointed out by Fuxe et al. (1978), there is little doubt that the 5HT and NE neurons are linked together neuroanatomically and that they influence one another at various points on the neural axis.