The substituted amphetamines 4-chloroamphetamine (PCA), 3,4-methylenedioxymethamphetamine (MDMA) and fenfluramine (FEN) share the common neurochemical action of acutely releasing central serotonin (5-HT), and yet their behavioral effects are quite different. The present study evaluated the effects of these compounds on acoustic and tactile startle reflexes. PCA and MDMA were qualitatively...
Activation of central serotonin 5HT2 receptors is believed to be the primary mechanism whereby lysergic acid diethylamide (LSD) and other hallucinogens induce psychoactive effects. This hypothesis is based on extensive radioligand binding and electrophysiological and behavioral studies in laboratory animals. However, the pharmacological profiles of 5HT2 and 5HT1C receptors are similar, making...
Abstract The Widely abused “designer” durg MDMA (3,4‐methylenedioxymethamphetamine) has been shown to caused marked and long‐lasting changes in brain serotonergic systems. The present study uses quantitative in vitro autoradiography of 3 H‐paroxetine labeled 5‐HT uptake sites to assess the time‐dependent effects of MDMA on 5‐HT neurons in specific neuroanatomic loci. Following treatment with...
The interactions of the indolealkylamine N,N-dimethyltryptamine (DMT) with 5-hydroxytryptamine1A (5-HT1A) and 5-HT2 receptors in rat brain were analyzed using radioligand binding techniques and biochemical functional assays. The affinity of DMT for 5-HT1A sites labeled by [3H]-8-hydroxy-2-(di-n-propylamino)tetralin ([3H]-8-OH-DPAT) was decreased in the presence of 10(-4) M GTP, suggesting...
The two major metabolites of (-+)3,4-methylenedioxyamphetamine (MDA), alpha-methyldopamine (a-MeDA) and 3-O-methyl-amethyldopamine (3-O-Me-a-MeDA), were administered to rats intracerebroventricularly and into brain parenchyma. In addition, their precursors, (a-MeDOPA and 3-O-Me-a-MeDOPA, respectively) were administered systemically, individually and in combination. None of these treatments...
Radioiodinated D-(+)-N1-ethyl-2-iodolysergic acid diethylamide ([125I]-EIL) has been evaluated as a ligand for in vitro and in vivo studies of cerebral serotonin 5-HT2 receptors. [125I]-EIL exhibited high affinity (KD = 209 pM) for 5-HT2 receptors with a high degree of specific binding (80-95%) in membranes from rat prefrontal cortex. The regional distribution of [125I]-EIL binding in vivo to...
Derivatives of amphetamine are potent releasers of both dopamine (DA) and serotonin (5-HT), but the relative contributions of DA and 5-HT release to the behavioral effects of these drugs have not been established. Previously, S-(+)3,4-methylenedioxymethamphetamine (S-(+)MDMA) was found to produce locomotor hyperactivity in rats which was dependent on 5-HT release. The present study found that...
Methylenedioxymethamphetamine (MDMA) produced a significant hyperthermia in rats which was antagonized in a competitive manner by the selective 5-HT2 antagonist, MDL 11,939. The 5-HT antagonist also blocked MDMA-induced neurotoxicity as assessed by the decline in regional 5-HT concentrations observed 1 week later. These two effects of MDL 11,939 were dissociated at higher doses of MDMA where...
In summary, the data from both neurochemical and neuroanatomical studies demonstrate widespread and long-lasting degeneration of serotonin neurons in brain without any major or consistent effects on catecholamine neurons following in vivo administration of MDMA in both rats and rhesus monkeys. A detailed examination of the parameters involved in the neurotoxic and neurodegenerative effects of...
Methylenedioxymethamphetamine (MDMA) is a phenylethylamine with novel mood-altering properties in humans. MDMA shares the dopamine-releasing properties of amphetamine but has been found to be a more potent releaser of serotonin (5-HT). The present study undertook to determine the relative roles of dopamine and 5-HT release in MDMA-induced locomotor hyperactivity. S-(+)MDMA produced...