Neurotransmitter

   Neurotransmitters are the chemicals involved in communication between nerve cells ("neurons"). Substances released from the end bulb of an upstream ("presynaptic") neuron into the synaptic space in order to excite or inhibit the downstream ("postsynaptic") neuron are called neurotransmitters. Although more than 100 chemicals have been identified as neurotransmitters, most research has been done on (1) acetylcholine (an ester of choline); (2) the "monoamine" neurotransmitters dopamine and norepinephrine; a monoamine contains one amino (NH) group; dopamine and norepinephrine are also called "catecholamines" because they have a "catechol" portion; (3) the monoamine neurotransmitters serotonin and melatonin, which are also called "indolamines" because of their "indole" portion; (4) the amino acid neurotransmitters such as gamma-aminobutyric acid, or GABA. (See Catecholamine Hypothesis of Depression; Dopamine; Synapse.)

   The chemicals that transmit the nerve impulse in the central nervous system were previously called "neurohormones," or "neurohumors," in a usage going back to Otto Loewi’s (1873–1961) expression "humoral transmission" in Pflügers Archiv in 1921. The term "neurotransmitter" became current in psychiatry in the 1960s, a foreshadowing of which is Ulf von Euler’s 1959 article on "Neurotransmission in the adrenergic nervous system" in the Harvey Lectures. (In the article, however, he refers to "nerve transmitter" rather than "neurotransmitter.")

   The substance Loewi discovered in 1921 was later identified as acetylcholine, the first neurotransmitter. (See Synapse.) In 1946, Ulf von Euler (1905–1983), professor of physiology at the Karolinska Institute in Stockholm, identified noradrenaline as the adrenergic neurotransmitter; he won a Nobel Prize for this in 1970. In 1957, Bernard B. Brodie (1909–1989) and Parkhurst A. Shore (1924–), in the Laboratory of Chemical Pharmacology of the National Heart Institute, part of the National Institutes of Health in Bethesda, Maryland, suggested that serotonin, or 5-hydroxytryptamine (5-HT) as it is also called, and norepinephrine functioned alike as "chemical mediators of mutually antagonistic centers in the brain." This proposal, in research published in the Annals of the New York Academy of Sciences, was tantamount to calling serotonin a neurotransmitter, although the authors used the phrase "central neurohumoral agent" (p. 631). Referring to the antagonism between serotonin and LSD, Brodie said, "It is probable that subtle biochemical events, peculiar to the brain, will ultimately explain normal brain function and the changes responsible for mental illnesses" (p. 641). (On LSD, see HALLUCINOGEN; on serotonin see Selective Serotonin Reuptake Inhibitors; on these events, see also Iproniazid.) In 1957, Swedish neuroscientist Arvid Carlsson (1923–) discovered the role of dopamine as a neurotransmitter, and published his work in Science in 1958 (the research had been submitted for publication in 1957, the true year of the discovery). Amino acids also function as neurotransmitters, in addition to the monoamine neurotransmitters and acetylcholine. The first amino acid to be identified as having a role in neurotransmission was gamma-aminobutyric acid (GABA), isolated in 1963 by Edward Arthur Kravitz (1932–) and co-workers at the National Institute of Neurological Disorders, in research published in the Journal of Neurophysiology. (In 1974, Solomon Snyder discovered the receptor for it.)

   In his Nobel Lecture in 2000, Carlsson observed, "During the past half-century brain research has been dominated by biochemical approaches. . . . [This] is understandable in view of the entrance of the neurohumoral transmission concept into brain research in conjunction with the spectacular progress of molecular biology. However, it must be recognized that the brain is not a chemical factory but an extremely complicated survival machine." Carlsson ventured that further progress in such areas as neuroimaging and pattern recognition "will help to reveal the enormous width of our present ignorance of the human brain" (Bioscience Reports, 2002, p. 707).