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Neuropsychopharmacology August 1999 George K. Aghajanian, Gerard J. Marek
This brief review traces the serotonin (5-HT) hypothesis of the action of hallucinogenic drugs from the early 1950s to the present day. There is now converging evidence from biochemical, electrophysiological, and behavioral studies that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and the phenethylamines (e.g., mescaline), have a common site of action as...
Neuropsychopharmacology August 1, 1999 J Backstrom 55 citations
For more than 40 years the hallucinogen lysergic acid diethylamide (LSD) has been known to modify serotonin neurotransmission. With the advent of molecular and cellular techniques, we are beginning to understand the complexity of LSD's actions at the serotonin 5-HT2 family of receptors. Here, we discuss evidence that signaling of LSD at 5-HT2C receptors differs from the endogenous agonist...
The British Journal of Psychiatry July 1, 1999 David M. Semple, Klaus P. Ebmeier, Michael F. Glabus et al. 281 citations
Background The use of MDMA (‘ecstasy’) is common among young people in Western countries. Animal models of MDMA toxicity suggest a loss of serotonergic neurons, and potentially implicate it in the development of significant psychiatric morbidity in humans. Aims To test whether long-term use of MDMA can produce abnormalities in cerebral serotonin, but not dopamine, transporter binding measured...
Journal of Neuroscience June 15, 1999 George Hatzidimitriou, Una D. Mccann, George A. Ricaurte 338 citations
The recreational drug (±)3,4-methylenedioxymethamphetamine (MDMA, “Ecstasy”) is a potent and selective brain serotonin (5-HT) neurotoxin in animals and, possibly, in humans. The purpose of the present study was to determine whether brain 5-HT deficits persist in squirrel monkeys beyond the 18-month period studied previously and to identify factors that influence recovery of injured 5-HT axons....
Neuropsychopharmacology May 1999 Franz X. Vollenweider, P Vontobel, Daniel Hell et al.
The modulating effects of serotonin on dopamine neurotransmission are not well understood, particularly in acute psychotic states. Positron emission tomography was used to examine the effect of psilocybin on the in vivo binding of [11C]raclopride to D2-dopamine receptors in the striatum in healthy volunteers after placebo and a psychotomimetic dose of psilocybin (n = 7). Psilocybin is a potent...
Journal of Biological Chemistry April 2, 1999 C. Niswender, Sara C. Copeland, K. Herrick‐Davis et al.
RNA transcripts encoding the serotonin 5-hydroxytryptamine 2C (5-HT2C) receptor (5-HT2CR) undergo adenosine-to-inosine RNA editing events at up to five specific sites. Compared with rat brain, human brain samples expressed higher levels of RNA transcripts encoding the amino acids valine-serine-valine (5-HT2C-VSV) and valine-glycine-valine (5-HT2C-VGV) at positions 156, 158, and 160,...
Brain Research April 1, 1999 George K. Aghajanian, Gerard J. Marek 379 citations
Previously, serotonin (5-HT) was found to induce a marked increase in glutamatergic spontaneous excitatory postsynaptic currents (EPSCs) in apical dendrites of layer V pyramidal cells of prefrontal cortex; this effect was mediated by 5-HT2A receptors, a proposed site of action of hallucinogenic and atypical antipsychotic drugs. Unexpectedly, although the effect of 5-HT was Ca2+-dependent and...
Brain Research Bulletin April 1, 1999 G B Wells, M C Lopez, J C Tanaka 30 citations
Ibogaine has been shown to affect biogenic amine levels in selected brain regions. Because of the involvement of these neurotransmitters in drug addiction, the effects of ibogaine on biogenic amine transport may contribute to the potential anti-addictive properties of ibogaine in vivo. With rat brain synaptosomes as our experimental system, we measured the effects of ibogaine on the uptake and...
Neuron March 1, 1999 R. Grailhe, C. Waeber, S. Dulawa et al.
In order to determine the distribution and function of the 5-HT5A serotonin receptor subtype, we generated knockout mice lacking the 5-HT5A gene. Comparative autoradiography studies of brains of wild-type (wt) and 5-HT5A knockout (5A-KO) mice revealed the existence of binding sites with high affinity for [125I]LSD that correspond to 5-HT5A receptors and that are concentrated in the olfactory...
Journal of Medicinal Chemistry March 1, 1999 Joseph B. Blair, Danuta Marona‐lewicka, Arthi Kanthasamy et al. 63 citations
The synthesis and biological activity of 6-[2-(N, N-dimethylamino)ethyl]-4H-thieno[3,2-b]pyrrole (3a) and 4-[2-(N, N-dimethylamino)ethyl]-6H-thieno[2,3-b]pyrrole (3b), thienopyrroles as potential bioisosteres of N,N-dimethyltryptamine (1a), are reported. Hallucinogen-like activity was evaluated in the two-lever drug discrimination paradigm using LSD- and DOI-trained rats. Neither 3a nor 3b...