Serotonin

Synthesis and biological evaluation of 2-(4-fluorophenoxy)-2-phenyl-ethyl piperazines as serotonin-selective reuptake inhibitors with a potentially improved adverse reaction profile

by Nicholas Cozzi

Rapid and efficient method for suspending cells for neurotransmitter uptake assays

by Nicholas Cozzi

Synthesis and pharmacological examination of benzofuran, indan, and tetralin analogues of 3,4-(methylenedioxy)amphetamine

by Nicholas Cozzi

Indan analogs of fenfluramine and norfenfluramine have reduced neurotoxic potential

by Nicholas Cozzi

Inhibition of plasma membrane monoamine transporters by β-ketoamphetamines

by Nicholas Cozzi

5HT 2A receptor antagonists inhibit potassium-stimulated γ-aminobutyric acid release in rat frontal cortex

by Nicholas Cozzi

Selective reduction of extracellular dopamine in the rat nucleus accumbens following chronic treatment with DAU 6215, a 5-HT3 receptor antagonist.

by Laura Pozzi

R Invernizzi, L Pozzi, R Samanin

Neuropharmacology (1995) Volume: 34, Issue: 2, Pages: 211-215

The effect of chronic treatment with (3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide chloride (DAU 6215; 15... more The effect of chronic treatment with (3-alpha-tropanyl)1H-benzimidazolone-3-carboxamide chloride (DAU 6215; 15 micrograms/kg s.c. twice daily for 21 days), a serotonin3 receptor antagonist, on the extracellular concentrations of dopamine (DA), dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) was studied by intracerebral dialysis in the striatum, nucleus accumbens and frontal cortex of conscious rats. Twenty-four hours after the last injection, the basal extracellular concentrations of DA in the nucleus accumbens of rats given DAU 6215 were significantly lower than in saline-treated rats. DA output in the dorsolateral striatum or frontal cortex was not significantly different between the DAU 6215 and saline-treated rats. Chronic DAU 6215 significantly reduced the extracellular concentrations of DOPAC and HVA in the frontal cortex but had no effect in the other brain regions. A subcutaneous challenge dose of DAU 6215 (15 micrograms/kg) did not significantly modify the extracellular concentrations of DA and its metabolites in either DAU 6215 or saline treated rats in any of the brain regions examined. The present investigation is the first on the effect of chronic administration of a 5-HT3 receptor antagonist on basal extracellular DA in the rat brain. The results provide evidence of an association between the electrophysiological and biochemical effects of chronic treatment with a serotonin3 receptor antagonist on the activity of the mesolimbic DA system. In line with the theory that hyperactivity of the mesolimbic dopaminergic system is involved in psychosis, the results suggest that DAU 6215 may be useful in the treatment of psychotic disorders, possibly with limited extrapyramidal effects

Stimulation of 5‐hydroxytryptamine (5‐HT2C) receptors in the ventrotegmental area inhibits stress‐induced but not basal dopamine release in the rat prefrontal cortex

by Laura Pozzi

Pozzi L, Acconcia S, Ceglia I, Invernizzi RW, Samanin R.

J Neurochem. 2002 Jul;82(1):93-100.

The present study investigated whether 5-HT(2C) receptors in the ventrotegmental area and prefrontal cortex regulate... more The present study investigated whether 5-HT(2C) receptors in the ventrotegmental area and prefrontal cortex regulate basal and stimulus-evoked dopamine release in the prefrontal cortex. Using the in vivo microdialysis technique in conscious rats, we studied the effect of a selective 5-HT(2C) receptor agonist, Ro60-0175, on basal and immobilization stress-induced dopamine release in the prefrontal cortex. Ro60-0175 intraperitoneally (2.5 mg/kg) and into the ventrotegmental area (10 microg/0.5 microL) completely antagonized the effect of stress on extracellular dopamine without altering basal levels. Infusion of 10 microm Ro60-0175 through the cortical probe had no significant effect on basal and stress-induced dopamine release. SB242084 (10 mg/kg), a selective antagonist of 5-HT(2C) receptors, significantly increased basal extracellular dopamine and completely prevented the effect of intraperitoneal and intraventrotegmental Ro60-0175 on the stress-induced rise of extracellular dopamine, but had no effect itself in stressed rats. The results show that Ro60-0175 suppresses cortical dopamine release induced by immobilization stress through the stimulation of 5-HT(2C) receptors in the ventrotegmental area. While confirming that endogenous 5-HT acting on 5-HT(2C) receptors tonically inhibit basal dopamine release in the prefrontal cortex, the present findings suggest that the stimulation of 5-HT(2C) receptors with an exogenous agonist preferentially inhibit stimulated release.

Lamoure J. How Do You Treat Internet Addiction. Cdn J of CME 2012; 24(3): 14

by Dr. Joel Lamoure

Lamoure J. How Do You Treat Internet Addiction. Cdn J of CME 2012; 24(3): 14

There are not many formats or forums at this point that address Internet addiction, and there is even some debate over... more There are not many formats or forums at this point that address Internet addiction, and there is even some debate over whether internet addiction is a true addiction. In my clinical experience and given definitions of addiction, "I would place internet as
being a very highly addictive medium."........

...... It provides a strong “hook” to those who are looking for a form of escapism. That being said, it is legal, cost effective, accessible, and provides instant gratification. It can, however, have a deleterious impact on the patient’s quality and quantity of life, with psychosocial retardation, financial challenges, and relationship challenges.

Much like patients with food or shopping addictions, there is the challenge that it cannot be easily extricated from daily life, especially in western and first/second world countries. Standard strategies that include removal of the offending agent will not work with internet addictions as there is exposure in insidious ways.......

From "Lamoure J. How Do You Treat Internet Addiction. Cdn J of CME 2012; 24(3): 14" (In press)

Dr. Joel W. Lamoure RPh., DD., FASCP
http://www.joelwlamoure.com/id6.html

Serotonin transporter polymorphism and borderline/antisocial traits among low-income young adults

by Bjarne Holmes

Combined effect of maternal serotonin transporter genotype and prenatal stress in modulating offspring social interaction in mice.

by Ryan Smith

Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum... more Several studies suggest that prenatal stress is a possible risk factor in the development of autism spectrum disorders. However, many children exposed to stress prenatally are born healthy and develop typically, suggesting that other factors must contribute to autism. Genes that contribute to stress reactivity may, therefore, exacerbate prenatal stress-mediated behavioral changes in the adult offspring. One candidate gene linked to increased stress reactivity encodes the serotonin transporter. Specifically, an insertion/deletion (long/short allele) polymorphism upstream of the serotonin transporter gene correlates with differential expression and function of the serotonin transporter and a heightened response to stressors. Heterozygous serotonin transporter knockout mice show reductions in serotonin transporter expression similar to the human short polymorphism. In this study, the role of prenatal stress and maternal serotonin transporter genotype were assessed in mice to determine whether their combined effect produces reductions in social behavior in the adult offspring. Pregnant serotonin transporter heterozygous knockout and wild-type dams were placed in either a control condition or subjected to chronic variable stress. The adult offspring were subsequently assessed for social interaction and anxiety using a three-chamber social approach task, ultrasonic vocalization detection, elevated-plus maze and an open field task. Results indicated that prenatal stress and reduced serotonin transporter expression of the dam may have the combined effect of producing changes in social interaction and social interest in the offspring consistent with those observed in autism spectrum disorder. This data indicates a possible combined effect of maternal serotonin transporter genotype and prenatal stress contributing to the production of autistic-like behaviors in offspring.

Caenorhabditis elegans selects distinct crawling and swimming gaits via dopamine and serotonin

by Andrés Vidal-Gadea

PNAS

Many animals, including humans, select alternate forms of motion (gaits) to move efficiently in different... more Many animals, including humans, select alternate forms of motion (gaits) to move efficiently in different environments. However, it is unclear whether primitive animals, such as nematodes, also use this strategy. We used a multifaceted approach to study how the nematode Caenorhabditis elegans freely moves into and out of water. We demonstrate that C. elegans uses biogenic amines to switch between distinct crawling and swimming gaits. Dopamine is necessary and sufficient to initiate and maintain crawling after swimming. Serotonin is necessary and sufficient to transition from crawling to swimming and to inhibit a set of crawl-specific behaviors. Further study of locomotory switching in C. elegans and its dependence on biogenic amines may provide insight into how gait transitions are performed in other animals.

Serotonergic Modulation of the Prefrontal Cortex: From Neurons to Brain Waves

by Vicky Puig

Book chapter in Psychiatric Disorders - Worldwide Advances, Toru Uehara (Ed.), ISBN: 978-953-307-833-5, InTech

Humans are remarkably proficient at some sophisticated and abstract tasks such as learning, memory and flexibility.... more Humans are remarkably proficient at some sophisticated and abstract tasks such as learning, memory and flexibility. These tasks depend on the prefrontal cortex, the cortical region most evolved in primates (Fuster, 2001; Miller & Cohen, 2001). The prefrontal cortex includes the most anterior structures of the frontal lobes, with some imprecise anatomical boundaries between different species of mammals. It has been defined across species according to its reciprocal anatomical connections with the mediodorsal nucleus of the thalamus (nucleus MD). The prefrontal cortex controls the activity of many subcortical structures via the excitatory axons of pyramidal neurons. These projection neurons forward the output signals of a complex cortical microcircuit composed of distinct types of excitatory pyramidal neurons and numerous types of inhibitory interneurons. It receives, along with the thalamus, dense innervation from many brain regions, including the serotonergic nuclei of the brainstem. During the last decade, research conducted by many laboratories has revealed that serotonin is a major modulator of prefrontal functions at the behavioral, neuronal and network levels. Its influences on cortical processing are implemented through multiple receptors expressed by pyramidal neurons as well as interneurons. These complex modulatory signals are altered in many psychiatric disorders such as schizophrenia and depression, where changes in receptor expression, neuron activity and brain waves have been observed. Furthermore, many psychiatric treatments -for instance, some antipsychotics and antidepressants- target the serotonergic system and the prefrontal cortex. Thus, understanding the role of serotonergic neurotransmission in prefrontal cortex function is of major importance. Here we present a summary of our findings on the anatomy, neurophysiology and pharmacology of the serotonergic system in the medial prefrontal cortex of the rat.

In vitro neuronal and vascular responses to 5‐HT in rats chronically exposed to MDMA

by Dara M Cannon

Serotonin transporter binding in major depressive disorder and bipolar disorder assessed using [11C] DASB and positron emission tomography

by Dara M Cannon

Differential effects of 5-HT2C receptor ligands on place conditioning and locomotor activity in rats

by dave hayes

Differential effects of 5-HT2C receptor activation by WAY 161503 on nicotine-induced place conditioning and locomotor activity in rats

by dave hayes

Effects of systemic and intra-nucleus accumbens 5-HT 2C receptor compounds on ventral tegmental area self-stimulation thresholds in rats

by dave hayes

Effects of systemic 5-HT1B receptor compounds on ventral tegmental area intracranial self-stimulation thresholds in rats

by dave hayes

The role of nucleus accumbens shell GABA receptors on ventral tegmental area intracranial self-stimulation and a potential role for the 5-HT2C receptor

by dave hayes