Catecholamines: Knowledge and understanding in the 1960s, now, and in the future

The late 1960s was a heyday for catecholamine research. Technological developments made it feasible to study the regulation of sympathetic neuronal transmission and to map the distribution of noradrenaline and dopamine in the brain. At last, it was possible to explain the mechanism of action of some important drugs that had been used in the clinic for more than a decade (e.g. the first generation of antidepressants) and to contemplate the rational development of new treatments (e.g. l-dihydroxyphenylalanine therapy, to compensate for the dopaminergic neuropathy in Parkinson’s disease, and β1-adrenoceptor antagonists as antihypertensives). The fact that drug targeting noradrenergic and/or dopaminergic transmission are still the first-line treatments for many psychiatric disorders (e.g. depression, schizophrenia, and attention deficit hyperactivity disorder) is a testament to the importance of these neurotransmitters and the research that has helped us to understand the regulation of their function. This article celebrates some of the highlights of research at that time, pays tribute to some of the subsequent landmark studies, and appraises the options for where it could go next.

Demonstration of Noradrenaline-Immunoreactive Nerve Fibres in the Liver

To demonstrate noradrenaline-immunoreactive nerve fibres in liver tissues, we used an antibody to noradrenaline in the immunostaining of liver tissues from rats, guinea-pigs and humans. The tissue specimens were fixed by perfusion or immersion with cacodylate buffer containing sodium metabisulphate and glutaraldehyde, and cryostat sections were prepared. An indirect peroxidase-labelled antibody method was used for staining noradrenaline. Noradrenaline-immunoreactive nerve fibres were localized around blood vessels in the portal area and around the central vein. There were differences between the species in the intralobular distribution of noradrenaline-immunoreactive fibres. Normal guinea-pig and human liver showed intralobular noradrenaline-immunoreactive fibres while rat liver did not. Noradrenaline-immunoreactive fibres were absent from regenerating nodules in a human cirrhotic liver. This method of demonstrating noradrenaline directly using perfusion- or immersion-fixation is appropriate for studying innervation in normal and damaged livers of various species including humans.