5-Hydroxytryptamine (5-HT, serotonin) type 3 (5-HT(3)) receptors belong to the alcohol-sensitive superfamily of Cys-loop ligand-gated ion channels, and they are thought to play an important role in alcoholism. Alcohols with small molecular volumes increase the amplitude of currents evoked by low 5-HT concentrations and shift the 5-HT concentration-response curve for 5-HT(3) receptor activation ...

Raphe and extra-raphe 5-HT-1A receptors contribute to feedback inhibition of serotonin (5-HT) neurons; however, the endogenous function of 5-HT-1A receptor-dependent feedback inhibition remains poorly understood. Here, the possibility that 5-HT-1A-mediated feedback inhibition of the raphe nuclei is topographically organized was examined. This was done by testing the effect of systemic blockade ...

We examined the in vivo effects of the hallucinogen 4-iodo-2,5-dimethoxyamphetamine (DOI). DOI suppressed the firing rate of 7 of 12 dorsal raphe (DR) serotonergic (5-HT) neurons and partially inhibited the rest (ED(50) = 20 microg/kg, i.v.), an effect reversed by M100907 (5-HT(2A) antagonist) and picrotoxinin (GABA(A) antagonist). DOI (1 mg/kg, s.c.) reduced the 5-HT release in medial prefront...

The post-transcriptional process of mRNA editing changes up to three amino acids in the second intracellular domain (i2) of the serotonin(2C) (5-HT(2C)) receptor and alters some signaling characteristics of the receptor. Here, we report that the substitution of valine for isoleucine (I156V; 5-HT(2C-VNI)), which occurs naturally as a result of mRNA editing, alters both ligand-dependent and -inde...

5-Hydroxytryptamine (5-HT; serotonin) is a potent vasoconstrictor and smooth muscle mitogen. Substances that produce similar responses also stimulate production of superoxide. We sought to determine whether 5-HT stimulates production of superoxide. 5-HT can be metabolized by cytochrome P450 to nitric oxide (NO), which scavenges superoxide. Thus, we hypothesized that inhibiting cytochrome P450 w...

This study investigates a number of parameters that influence the neurotoxic effects of 3,4-methylenedioxymethamphetamine (MDMA) on serotonin (5-HT) neurons in brain. Both the dose and number of injections of MDMA affect the degree of neurotoxicity on 5-HT axons and terminals as assessed by decreases in the content of 5-HT and 5-hydroxyindoleacetic acid (5-HIAA) and the density of 5-HT uptake s...

BACKGROUND Clinical success with modern heart transplantation (HT) has led to the development of an alternate list (AL) HT strategy, matching marginal cardiac allografts with recipients who do not meet standard criteria for HT. Marginal allografts may be at an increased risk for primary graft dysfunction (PGD), the leading cause of early mortality after HT.(1) The incidence of PGD in AL HT rela...

BACKGROUND The survival benefit of heart transplantation (HT) compared with optimal medical therapy (OMT) has never been tested. METHODS AND RESULTS We created a decision analytic model that simulates a randomized clinical trial of OMT versus HT for each New York Heart Association (NYHA) class. The simulation calculates average life expectancy. The following assumptions were made for OMT annu...

Dyskinesia seen in the off-state, referred as graft-induced dyskinesia (GID), has emerged as a serious complication induced by dopamine (DA) cell transplantation in parkinsonian patients. Although the mechanism underlying the appearance of GID is unknown, in a recent clinical study the partial 5-HT(1A) agonist buspirone was found to markedly reduce GID in three grafted patients, who showed sign...

1. The properties of membrane currents that were modulated by serotonin (5-HT) were investigated with two-electrode voltage-clamp techniques in sensory neuron somata isolated from the pleural ganglion of Aplysia californica. The modulatory effects of 5-HT were revealed by computer subtraction of current responses elicited in the presence of 5-HT from current responses elicited prior to the appl...