Arvid Carlsson – Wikipedia

Arvid Carlsson (Uppsala, January 25, 1923 – Gothenburg, 29 June 2018) was a Swedish doctor and neuroscientist.

Arvid Carlsoon graduated in 1951 from the University of Lund (Sweden) where in 1956 he became a professor of pharmacology. In 1959 he obtained the role of professor and principal at the Pharmacology department at the University of Gothenburg. In 1979 he received the Wolf Prize for Medicine together with Roger Wolcott Sperry and Oleh Hornykiewicz for his work on the role of dopamine as a neurotransmitter and wins the Nobel Prize for Medicine in 2000 together with Eric Kandel and Paul Greengard ^[first] for the discoveries relating to the signals of transduction in the nervous system. It is one of the greatest neuroscientists of the past century.

Born in Uppsala, Sweden, on January 25, 1923, he grew up in a wealthy family in which much importance is given to academic study ^[2] ; His father Gottfrid Carlsson gets the chair of history at the University of Lund ^[2] . Her mother, although she graduated in letters, gave up everything for the growth of children and assistance to her husband in her studies. After the death of her husband, she devoted herself to the legal state of Swedish women in the Middle Ages, publishing some books and receiving a degree to honor in philosophy at the University of Uppsala ^[2] .
Arvid, third of four children, unlike the brothers who graduate in letters ^[2] It is dedicated to medicine for the belief that sciences can be more useful than humanities ^[2] .
At the age of 16, in June 1939, two and a half months before the outbreak of the Second World War, he made a tour of self -lace for Germany lasting two weeks. In this way he has the opportunity to meet people of different status and social conditions and their ideas about the imminent catastrophe that would have upset the world (Second World War) ^[2] . On 22/10/2005 he received the Honoris Causa degree in Medicine and Surgery, at the University of Catania, under the rectorate of F. Lattori. ^[3]

He began his medical studies at the University of Lund in 1941, interrupted for a few years by military service ^[4] . Lund is a university town, a small reminiscence of Oxford ^[4] . The quality of research and teaching was good as evidenced by the presence of some important figures such as: Torsten Thunberg, Ernest Overton, Nils Alwall, and many others.
During his first years of studies, the Second World War makes Sweden almost completely isolated, but despite this five Danish medical students, forced to leave Denmark in that period occupied by Germany, come to Lund to carry out their anatomical studies ^[4] . In this way Arvid meets Ib Munkvad (he also tells of their chess games ^[4] ) then became one of the most important biological psychiatrists of Denmark. Another important event that occurred during the war occurs in October 1943 when thousands of Jews manage to escape on small fishing boats from Denmark avoiding deportation to the German concentration camps. Among these Jews there was a number of important researchers who were immediately enrolled in the medical school where they became important teachers and scholars ^[5] .

In 1944, he became assistant pharmacology assistant at the University of Lund, after successfully passing the exam in that discipline ^[5] . The head of this department, and at the same time unique professor, was Gunnar Ahlgren, who commissioned Arvid and Georg Theander a topic on the duration of the action of PentileneTrazole (Cardiazol), a convulsive later frequently used as an analectic to awaken falling people In overdose of hypnotic or sedative and as a precursor of electroconvulsive therapy ^[5] . Thus they discover that the increase under partial pressure of nitrogen oxide can be used to measure the action of the repentance. Thanks to these studies they have received a modest prize, intended for young medical researchers of the University of Lund ^[6] . Together with another pharmacologist, Folke Serin, Carlsson studies the action of another analectic, Tharide And they discover a circadian rhythm in its lethal action. The publication of these discoveries (Carlsonn and Serin 1950) seems to be the first to have described a circadian rhythm in the action of a medicine, according to recent articles of Chronobiology ^[6] .

Calcium metabolism [ change | Modifica Wikitesto ]

In 1948 Gunnar Ahlgren convinced Carlsson to try a new research area together with his colleague Georg Theander: the metabolism of football. At that time, radioactive traces of the carbon isotope 45 become commercially available; Arvid and Georg agree to test football salts for some clinical exams for a Swedish pharmaceutical house ^[6] And even if this research does not reveal anything interesting, they decide to use this opportunity to study the absorption of calcium and its metabolism in the skeleton ^[6] . Among other things, they discover that vitamin D in physiological doses can stimulate not only intestinal absorption and growth but also the reabsorption of bone mineral ^[6] . These first discoveries cause international interest and both are invited to the Gordon Conference in the summer of 1955.

Not having received the university chair of Pharmacology in Lund in 1952, Arvid decides to leave the pharmacology and devote himself to internal medicine ^[6] . However, the basic research was too interesting to be completely abandoned and asks Sune Bergström, professor of chemical medicine, if there was the possibility of working in an American laboratory, studying chemical pharmacology ^[7] . In August 1955, after attending the Gordon Conference on Mineral metabolism , he begins to work in the laboratory of Dr. Brodie: the Laboraty of Chemical Pharmacology at the National Heart Institute of the National Institutes of Health in Bethesda, Maryland. He performs studies with Brodie and Parkhurst A. Shore on the effects of the renovation and on the deposit of serotonin in the blood grown in vitro ^[7] . After a month of completely negative results, the “in vitro” system begins to work better thanks to the arrival of a new lot of reservoir. So he manages to demonstrate the presence of a clear and specific block with very low concentrations of reservoir in the serotonin deposit in cultivation. This is the first demonstration of the direct action of the renovation on the Serotonin deposit ^[7] . In a truly extraordinary period for medical research and psychopharmacology, Carlsson thanks to Brodie and Shore, comes into contact with the most modern methods of biochemical pharmacology and the psychopharmacology of time ^[8] .

Return to Sweden: I work on the dopa and dopamine reservoir [ change | Modifica Wikitesto ]

After spending 5 fruitful months in the Brodie laboratory, he returned to Lund, having been appointed associate professor of pharmacology. Together with Nils-Ake Hillarp he discovers that the reservoir causes the exhaustion of adrenal hormones (Carlsson and Hillarp, ​​1956) ^[8] And shortly thereafter, together with the students Ake Bertler and Evald Rosengren, that such exhaustion also takes place in other fabrics such as the brain ^[9] . These discoveries offer a possible explanation to the hypothetical action of the reservoir as they seem to confirm some experiments he made ^[ten] . Furthermore, the hypotensive action of the medicine is due to the effect on the catecholamines which in turn is based on exhaustion rather than on the release of serotonin ^[11] .
To better understand the action of the Remerpine, Carlsson and its collaborators administer 3.4-Dihydossifenilalanine (Dopa) to rabbits and rats treated with the reservoir and discover the main stimulating action of this amino acid as well as its ability to store sedative action and acinesic of the reservo ^[9] . They also suggest that the exhaustion of catecholamine, rather than serotonin, is responsible for some important behavioral effects of the reservoir ^[9] . Further analyzes reveal that the Dopa action is closely related to the accumulation in the dopamine brain which is its fundamental component ^[11] . The data suggest that dopamine is not a precursor of norepinephrine, as it was commonly believed at that time, but a variable ^[11] . The important studies on Parkinson’s induced by the reservoir reveal the depletion of dopamine, implicated in the control of extrapyramidal motor functions, which can be reinstated by the L-Dopa.
However, these discoveries were not initially and uniquely accepted; They were even considered useless and to be forgotten during the Ciba Symposium which was held in the summer of 1960 ^[twelfth] .

Chemical transmission in the brain and emerging synaphology [ change | Modifica Wikitesto ]

At the beginning of the 1960s, a large number of observations were made in Sweden by Carlsson and Hillarp and their respective collaborators, based on the combination of histochimic, biochemistry and functional studies ^[13] ; They also use a large number of new pharmacological tools. These observations contribute to convincing the scientific community of the role of bigenic amines as neurotransmitters and chemical transmission as an important physiological principle of the brain ^[14] . Carlsson’s group reaches a new model of Sinapsi; In fact, they are convinced that granules are essential in the nervous transmission, and that transmitters must be reliable so that they become available for the release of the nervous impulse. Further studies lead to the discovery of the way of acting of the main antiseptic agents such as chlorpromazine and haloperiodolus, which have a clinical and pharmacological profile similar to reservoir, even if they differ in the absence of monoamine reduction properties ^[15] ; The main antipsychotic drugs, instead of reducing the availability of monoamine, block the receptors involved in the transmission of dopamine and norepinephrine ^[16] . Arvid also carried out studies on the Reward System and toxicodedness ^[17] . That dopamine plays a crucial role in these two aspects is now commonly recognized but at the time it was not so simple and Carlsson’s research group is interested in this problem in the mid -1960s; They discover that the amphetamine releases dopamine and that its stimulating action can be blocked by an inhibitor of catecholamin synthesis, α-metaltyrosine ^[17] . Continuing on this line, you reach the idea that dopamine is also involved in psychostimulants and the abuse of many other heavier drugs, such as opiates and ethanol, causes dependence ^[17] .

The discovery of dopaminergic receptors and their potential role [ change | Modifica Wikitesto ]

After developing a method for measuring the limiting factor in the synthesis of catecholamine in vivo, Arvid discovers that the dopamine synthesis can be inhibited by an agonist dopamine receptor and stimulated by an antagonist ^[17] . Thus comes to the conclusion that the receptors involved are pre -rage and to avoid confusion about their nature, he decides to call them self -employers ^[18] . It also discovers that low doses of agonist dopaminergic receptors can have a preferential action on self -employers and thus cause a paradoxical behavioral inhibition ^[18] . Four years later, the collaboration with organic chemists led to the discovery of the 3-App and the different functions due to the positive or negative character of this agent ^[18] . In 1986, he received a letter from Carol Tammina of Maryland Psychiatric Research Center, in which he asked to test (-) 3-app on patients with schizophrenia. The results ascertain that a week of treatment with (-) 3-app causes a significant psychotic response, but the therapeutic effect does not last more than 2 or 3 weeks. In fact, the (-) 3-app is ancient on the rats and a slight anti-parkinson action has been demonstrated in clinical studies ^[19] .

Arvid Carlsson was involved in research projects together with 5 different pharmaceutical industries from 1960 onwards. Of particular importance in the initial phase was the collaboration with Hässle, an Astra Company consociatory ^[20] . The Astra Group as a whole grew a lot to the point that beta-blockers such as the metroprolol Beta-1 antagonist, they were almost all marketed by it ^[21] .
From a scientific point of view, the most important result of the collaboration with Hässle and Astra, was the development of the first SSRI, Zimelidine ^[22] . Carlsoon thus develops the first dopamine self-employer both agonist and antagonist, as well as the first selective competitive receptor 8-hydroxy-dpat. In 1987, a fruitful collaboration began with the Upjohn Company, a collaboration that lasts seven years ^[23] . It is during this period that it also manages to develop the concept of thalamic filter mechanism and interaction between neurotransmitters in neuronal circuits. At the end of the collaboration with Upjohn in 1994, Carlsson managed to keep his two research groups intact, the pharmacological and chemical groups, thanks to the collaboration with three other pharmaceutical companies ^[23] . Among the latter, the one with Hoechst Marion Roustell (once Marion Merrell Dow ) has been underway for more time.

Year	Prizes and congresses
1947	Magnus Blix ‘Prize, Univ. Of Lund, Sweden.
1970	“First Annual James Parkinson Lecture and Award”, Parkinson’s Disease Foundation, New York.
	“Pehr Dubb’s Gold Medal, for research in neurochemistry, The Medical Society of Gothenburg.
1973	“Second Annual Grass Foundation Lecture”, Society for Neuroscience in San Diego, California.
1974	“Anders years Medical Prize” University of Oslo, Norway.
1975	“Stanley R. Dean Lecture and Award, American College of Psychiatrists, Phoenix, Arizona.
	“Anna-Monika Stiftung, 1st Prize”, Munich, for research on antidepressants and neuroleptics.
1978	His Majesty, The King’s of Sweden Medal.
1979	“Wolf Prize in Medicine”, Jerusalem, Israel (together with R.W. Sperry and O. Hornykiewicz).
1981	“Björkénska Prize”, Univ. Of Uppsala, Sweden.
	“The Thomas William Salmon Lectures and Medal”, New York.
1982	“Gairdner Foundation Award”, Toronto, Canada.
1985	“Hilda and Alfred Eriksson’s Prize”, The Royal Swedish Academy of Science.
	“Senator Dr. Franz Burda Stiftung”, Vienna, Austria, for Research on Parkinson’s Disease.
1986	The Medal of Helsinki University, Finland.
1988	“Annual Neurobiology Lectureship Award, Univ. of Lund, Sweden. The “Jubileumspris” of the Swedish Medical Association.
1989	“Distinguished Lecture Series”, Irvine Neuroscience Association, Irvine, California.
	“The Second Annual Bristol-Myers Award for Distinguished Achievement in Neuroscience Research”, New York (together with J. Axelrod and P. Greengard).
	“Varro E. Tyler Distinguished Lectureship”, Purdue University, West Lafayette, Indiana.
1990	“The Paul Hoch Prize”, American Psychopathological Association, New York.
	“The Fred Springer Award”, American Parkinson Disease Association, Miami, Florida.
1991	“William K. Warren Schizophrenia Research Award, Tucson, Arizona.
1992	The “Open Mind Award in Psychiatry”, Janssen Research Foundation, Paris, France, together with H. Hippius and H. van Praag.
	The “Julius Axelrod Medal”, The Catecholamine Club, Anaheim, California.
1993	Lilly Lecture, Indianapolis, Indiana.
1994	Albert Barrett Memorial Lecture, Univ. of Michigan.
	The Japan Prize, in Psychology and Psychiatry, The Science and Technology Foundation of Japan.
	The “Lieber Prize” for research in schizophrenia, given by the Scientific Council of The National Alliance for Research in Schizophrenia and Depression, USA.
1995	The Research Prize of the Lundbeck Foundation, Roskilde, Denmark. The Robert J and Claire Pasarow Foundation Award for Neuropsychiatric Research. L.A., USA.
	Synthelabo Lecture, VIII ECNP Congress, Venice.
1996	Plaque for “Lifetime Achievement”. American Society of Biological Psychiatry.
	Gold Medal and Honorary Diploma, The Swedish Parkinson Association.
1997	Craepelin medal in gold. Max Planck Institute for Psychiatry, Munich, Germany.
1998	Gold Medal, Soc. of Biol. Psychiatry, Toronto, Canada.
1999	Gold Medal, Distinguished Lecture and Award, Univ. of Bari, Italy.
	Feltrinelli International Prize, Accademia dei Lincei, Rome. [25]
2000	Nobel Prize in Medicine or Physiology.

Year	Honorary degrees
1976	M.D. Honorary, Univ. of Cagliari, Italy.
1977	Doctor of Pharmacy Honoris Causa, Univ. of Uppsala, Sweden.
1990	Ph.D. Honorary, Univ. HELSINKI, Finland.
1991	Dr. rer. physiol. honoris causa, Univ. of Marburg, Germany

Year	Membership
1962	Member of the Collegium Internationale Neuro-Psychopharmacologicum (President 1978-1980).
1968	Member of the Royal Society for Science and Arts in Gothenburg.
1972	Foreign Member of the Japanese Pharmacological Society.
1974	Foreign Member of the American College of Neuropsychopharmacology.
	Corresponding Member of the German Pharmacological Society
1975	Member of the Royal Swedish Academy of Sciences.
1983	Honorary Fellow of The Medical Society of Gothenburg
1898	Member of the Academia Europaea.
1991	Honorary Fellow of the World Federation of Societies of Biological Psychiatry.
1992	Honorary Fellow of the Collegium Internationale Neuro-Psychopharmacologicum.
	Honorary Fellow of Academia medical and psychiatriae.
1996	Foreign Associate Member of The Institute of Medicine, National Academy of Sciences, U.S.A.
1997	Honorary Fellow of the Swedish Society of Biological Psychiatry.
1998	Honorary Member of the German Society of Biological Psychiatry.
1999	Honorary Member of the Scandinavian Society for Psychopharmacology.
2000	Honorary Member of “Parkinson’s Association in Western Sweden”.

• Arvid Carlsson , Metabolism of Radiocalcium in Relation to Calcium Intake in Young Rats , Berlingska Boktr., 1951, pp 74
• Arvid Carlsson with Bengt Falck and Nils-Aake Hillarp , Cellular Localization of Brain Monoamines , Berlingska Book Printing, 1962, PP 28
• Arvid Carlsson with Nils-Ake Hillarp and Bertil Waldeck , Analysis of the Mgtt-ATP Dependent Storage Mechanism in the Amine Granules of the Adrenal Medulla (1963), pp 38
• Arvid Carlsson Kurt, Jellinger E Peter Riederer , Current Topics in Extrapyramidal Disorders , Springer-Verlag, 1980, PP 241
• Arvid Carlsson with Lena Carlsson , Messengers of the Brain , Education House/Student Literature, 2002, PP 199
• Arvid Carlsson and Yves Lecrubier , Progress in Dopamine Research Schizophrenia: A Guide for Physicians , Taylor & Francis Group, 2004, pp 128

• Arvid Carlsson, in Larry R. Squire (the care of), The Hystory of Neuroscience in Autobiography , Volume 2, Academic Press, UNITED STATES OF AMERICA, 1998, pp 28–66
• Arvid Carlsson, A Half-Century of Neurotransmitter Research: Impact on Neurology and Psychiatry (Nobel Lecture), Chembiochem, 2001.