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.

https://science.sciencemag.org/content/sci/274/5292/1527.full.pdf

Association of Anxiety-Related Traits with a Polymorphism in the Serotonin Transporter Gene Regulatory Region

A review of central 5-HT receptors and their function

http://www.back-in-business-physiotherapy.com/images/files/DescendingControl.pdf

Descending control of pain.

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.

https://science.sciencemag.org/content/sci/278/5335/52.full.pdf

Drug Abuse: Hedonic Homeostatic Dysregulation

The locus coeruleus-noradrenergic system: modulation of behavioral state and state-dependent cognitive processes.

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.

Floyd E. Bloom

Papers

Psychopharmacology: The Fourth Generation of Progress