278 KOPIN
the major means of terminating the action of these catecholamines.
But at nerve endings, that is not the case. The proof that reuptake into
the sympathetic nerve terminals was the major means for terminating
the actions of norepinephrine released at the nerve terminals was ob
tained with radioactive norepinephrine. If the nerves degenerated, the
norepinephrine was not taken up into the tissues. Hertting, the Visiting
Scientist who was then working in Axelrod’s laboratory, and I performed
the experiment in which a cat’s right superior cervical ganglion was
removed. A week later, after the sympathetic nerves had degenerated,
almost no administered radioactivity was found in the denervated
tissues, indicating the importance of the nerves for accumulating the
catecholamine. This, along with the known supersensitivity of dener
vated tissues exposed to catecholamines, indicated the physiological
importance of the uptake process. This was further supported when it
was demonstrated that cocaine-induced supersensitivity to catechola
mines was attended by a blockade of the neuronal uptake process.
Arvid Carlsson was also at this symposium, where he first presented
the observations that were the basis for his Nobel Prize in 2000. He
showed that dopamine was present in the corpus striatum, that when
reserpine depleted the content of dopamine in the brain, the animal
appeared Parkinsonian, and that the behavioral motor deficit could be
reversed by treatment with the dopamine precursor, dihydroxypheny
lalanine (DOPA). The essentials for DOPA treatment of human Parkinson’s
disease were there, but it was not until ten years later, in 1968, that George
Cotzias successfully treated patients with sufficiently high doses of
DOPA to obtain therapeutic effects on the motor deficits.
Kety, in providing an overview of the symposium and the central
actions of catecholamines, wrote “In biochemistry as well as pharma
cology, the brain is often the last organ to be tackled and will certainly
be the last to be understood.”^6 This is as true today as it was then. We are
still looking for answers about the biological bases for mental disease;
the role of molecules in the brain is still a challenging problem. Many
Nobel Prizes are awaiting the scientists who unravel these perplexing
processes that regulate brain function, but I think it unlikely that there
will be a symposium in which as many as five future Nobel Prize laure
ates will participate.^7