Book•
Psychopharmacology: The Fourth Generation of Progress
15 Jan 1995-
TL;DR: Part 1 Preclinical section: critical analysis of methods transmitter systems - amino acids, amines, peptides, new transmitterscritical analysis of integrative concepts.
Abstract: Part 1 Preclinical section: critical analysis of methods transmitter systems - amino acids, amines, peptides, new transmitters critical analysis of integrative concepts. Part 2 Clinical section: critical analysis of methods psychiatric disorders - mood disorders, schizophrenia, anxiety disorders geriatric disorders neuroleptic disorders tardive dyskinesias AIDS personality disorders eating and sleeping disorders childhood disorders substance abuse critical analysis of integrative concepts. Part 3 Special topics.
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TL;DR: The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5HTT expression and 5HT uptake in lymphoblasts as discussed by the authors, which is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs.
Abstract: Transporter-facilitated uptake of serotonin (5-hydroxytryptamine or 5-HT) has been implicated in anxiety in humans and animal models and is the site of action of widely used uptake-inhibiting antidepressant and antianxiety drugs. Human 5-HT transporter (5-HTT) gene transcription is modulated by a common polymorphism in its upstream regulatory region. The short variant of the polymorphism reduces the transcriptional efficiency of the 5-HTT gene promoter, resulting in decreased 5-HTT expression and 5-HT uptake in lymphoblasts. Association studies in two independent samples totaling 505 individuals revealed that the 5-HTT polymorphism accounts for 3 to 4 percent of total variation and 7 to 9 percent of inherited variance in anxiety-related personality traits in individuals as well as sibships.
5,072 citations
TL;DR: A number of 5-HT receptor ligands are currently utilised, or are in clinical development, to reduce the symptoms of CNS dysfunction and the functional responses attributed to each receptor in the brain are reviewed.
3,074 citations
TL;DR: The present review focuses on the organisation of descending pathways and their pathophysiological significance, the role of individual transmitters and specific receptor types in the modulation and expression of mechanisms of descending inhibition and facilitation and the advantages and limitations of established and innovative analgesic strategies which act by manipulation of descending controls.
2,565 citations
TL;DR: This framework provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and to relapse in individuals with a history of addiction.
Abstract: Understanding the neurobiological mechanisms of addiction requires an integration of basic neuroscience with social psychology, experimental psychology, and psychiatry. Addiction is presented as a cycle of spiralling dysregulation of brain reward systems that progressively increases, resulting in compulsive drug use and a loss of control over drug-taking. Sensitization and counteradaptation are hypothesized to contribute to this hedonic homeostatic dysregulation, and the neurobiological mechanisms involved, such as the mesolimbic dopamine system, opioid peptidergic systems, and brain and hormonal stress systems, are beginning to be characterized. This framework provides a realistic approach to identifying the neurobiological factors that produce vulnerability to addiction and to relapse in individuals with a history of addiction.
2,391 citations
TL;DR: It is suggested that dysregulation of locus coeruleus-noradrenergic neurotransmission may contribute to cognitive and/or arousal dysfunction associated with a variety of psychiatric disorders, including attention-deficit hyperactivity disorder, sleep and arousal disorders, as well as certain affective Disorders, including post-traumatic stress disorder.
2,207 citations