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Birth of neuropsychopharmacology– impact on brain research
Brain Research Bulletin, Vol. 50, Nos. 5/6, p. 363, 1999 Copyright © 1999 Elsevier Science Inc. Printed in the USA. All rights reserved 0361-9230/99/$–see front matter
PII S0361-9230(99)00106-9
Birth of neuropsychopharmacology– impact on brain research Arvid Carlsson* Department of Pharmacology, University of Go¨teborg, Go¨teborg, Sweden [Received 12 April 1999; Accepted 20 April 1999] synaptology led to the elucidation of the mode of action of major psychopharmacological agents. For example, antipsychotic agents such as chlorpromazine and haloperidol, were shown to act by blocking receptors for dopamine and related compounds, and the tricyclic antidepressant drugs were shown to block the reuptake of noradrenaline and serotonin [1]. These break-through discoveries have had a tremendous impact on brain research. The number of established and potential neurotransmitters increased dramatically, and practically every aspect of brain function could be further clarified by applying the concept of chemical transmission and the use of probes permitting the perturbation of neurotransmitter function. The impact on both basic and clinical brain research has been considerable. Clinically, new pathophysiological hypotheses regarding major neurological and psychiatric disorders have greatly stimulated neuropsychiatric research. In addition, a large number of new diagnostic and therapeutic approaches have been initiated. Novel therapeutic principles have been developed. For example, the selective serotonin reuptake inhibitors (SSRIs) and a new generation of antipsychotic agents with improved therapeutic efficacy and less serious side effects have been introduced. Several agents acting on entirely new targets are in the pipeline and offer great promise for the treatment of an array of neuropsychiatric disorders [2].
Today the concept of chemical neurotransmission is the backbone of brain research. Although this theory goes back to the beginning of the twentieth century, it did not receive direct experimental support until the 1920s, and it took another several decades until its fundamental role in brain function started to be generally recognized. For a long time the transfer of information between brain neurons was believed to occur mainly, if not exclusively, through electrical signals. This was in contrast to the peripheral nervous system, where the concept of chemical transmission had gained general acceptance already before 1950. It was the break-through discovery of novel psychopharmacological agents in the 1950s and the ensuing birth of modern neuropsychopharmacology that paved the way for the penetration of the concept of chemical transmission into the brain. Although the occurrence of, for example, noradrenaline and serotonin in the brain could be demonstrated around the middle of the century, many leaders in neurotransmitter research expressed serious doubt about their functional role as late as 1960. A shift in basic thinking took its origin in 1955 when Bernard B. Brodie and his colleagues discovered the ability of reserpine, a newly discovered antipsychotic agent, to cause depletion of serotonin from its stores in various tissues, including the brain [3]. This was soon followed by the discovery that this agent has a similar action on the catecholamines. Subsequently, a dramatic escalation of research into the mode of action of psychopharmacological agents took place. This was triggered by the discovery of dopamine in the brain and the elucidation of its role in mental and motor functions. Doubts about the neurotransmitter function of these amines were dissipated by the development of histochemical techniques that permitted the demonstration of their occurrence in specific nerve tracts. The mapping of monoaminergic nerve tracts as well as the emerging
REFERENCES 1. Carlsson, A. Perspectives on the discovery of central monoaminergic neurotransmission. Ann. Rev. Neurosci. 10:19 – 40; 1987. 2. Carlsson, A. Early psychopharmacology and the rise of modern brain research. J. Psychopharmacol. 4:120 –126; 1990. 3. Pletscher, A.; Shore, P. A.; Brodie, B. B. Serotonin release as a possible mechanism of reserpine action. Science 122:374 –375; 1955.
* Address for correspondence: Prof. Arvid Carlsson, Dept. of Pharmacology, University of Go¨teborg, Box 431, SE 405 30 Go¨teborg, Sweden. Fax: ⫹46-31-82 17 95; E-mail: [email protected]
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PII S0361-9230(99)00106-9
Birth of neuropsychopharmacology– impact on brain research Arvid Carlsson* Department of Pharmacology, University of Go¨teborg, Go¨teborg, Sweden [Received 12 April 1999; Accepted 20 April 1999] synaptology led to the elucidation of the mode of action of major psychopharmacological agents. For example, antipsychotic agents such as chlorpromazine and haloperidol, were shown to act by blocking receptors for dopamine and related compounds, and the tricyclic antidepressant drugs were shown to block the reuptake of noradrenaline and serotonin [1]. These break-through discoveries have had a tremendous impact on brain research. The number of established and potential neurotransmitters increased dramatically, and practically every aspect of brain function could be further clarified by applying the concept of chemical transmission and the use of probes permitting the perturbation of neurotransmitter function. The impact on both basic and clinical brain research has been considerable. Clinically, new pathophysiological hypotheses regarding major neurological and psychiatric disorders have greatly stimulated neuropsychiatric research. In addition, a large number of new diagnostic and therapeutic approaches have been initiated. Novel therapeutic principles have been developed. For example, the selective serotonin reuptake inhibitors (SSRIs) and a new generation of antipsychotic agents with improved therapeutic efficacy and less serious side effects have been introduced. Several agents acting on entirely new targets are in the pipeline and offer great promise for the treatment of an array of neuropsychiatric disorders [2].
Today the concept of chemical neurotransmission is the backbone of brain research. Although this theory goes back to the beginning of the twentieth century, it did not receive direct experimental support until the 1920s, and it took another several decades until its fundamental role in brain function started to be generally recognized. For a long time the transfer of information between brain neurons was believed to occur mainly, if not exclusively, through electrical signals. This was in contrast to the peripheral nervous system, where the concept of chemical transmission had gained general acceptance already before 1950. It was the break-through discovery of novel psychopharmacological agents in the 1950s and the ensuing birth of modern neuropsychopharmacology that paved the way for the penetration of the concept of chemical transmission into the brain. Although the occurrence of, for example, noradrenaline and serotonin in the brain could be demonstrated around the middle of the century, many leaders in neurotransmitter research expressed serious doubt about their functional role as late as 1960. A shift in basic thinking took its origin in 1955 when Bernard B. Brodie and his colleagues discovered the ability of reserpine, a newly discovered antipsychotic agent, to cause depletion of serotonin from its stores in various tissues, including the brain [3]. This was soon followed by the discovery that this agent has a similar action on the catecholamines. Subsequently, a dramatic escalation of research into the mode of action of psychopharmacological agents took place. This was triggered by the discovery of dopamine in the brain and the elucidation of its role in mental and motor functions. Doubts about the neurotransmitter function of these amines were dissipated by the development of histochemical techniques that permitted the demonstration of their occurrence in specific nerve tracts. The mapping of monoaminergic nerve tracts as well as the emerging
REFERENCES 1. Carlsson, A. Perspectives on the discovery of central monoaminergic neurotransmission. Ann. Rev. Neurosci. 10:19 – 40; 1987. 2. Carlsson, A. Early psychopharmacology and the rise of modern brain research. J. Psychopharmacol. 4:120 –126; 1990. 3. Pletscher, A.; Shore, P. A.; Brodie, B. B. Serotonin release as a possible mechanism of reserpine action. Science 122:374 –375; 1955.
* Address for correspondence: Prof. Arvid Carlsson, Dept. of Pharmacology, University of Go¨teborg, Box 431, SE 405 30 Go¨teborg, Sweden. Fax: ⫹46-31-82 17 95; E-mail: [email protected]
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