Abstract Activation of mGluR2 (metabotropic glutamate receptor 2), the primary presynaptic autoreceptor for glutamate in the brain, is well established to attenuate the psychedelics-mediated behavioral and electrophysiological effects. However, the mechanisms responsible for these actions are controversial. The two competing mechanistic hypotheses have been proposed to explain this phenomenon...
Background: The treatment of major depressive disorder (MDD) with available antidepressant drugs is characterized by considerable ineffectiveness. Classical psychedelics such as psilocybin and N,N-dimethyltryptamine (DMT), which act primarily as 5-hydroxytryptamine 2A (5-HT 2A ) receptor agonists, have shown preliminary efficacy for inducing long-term remission in MDD after one or two doses....
There is substantial evidence that glutamate can modulate the effects of 5-hydroxytryptamine2A (5-HT2A) receptor activation through stimulation of metabotropic glutamate 2/3 (mGlu2/3) receptors in the prefrontal cortex. Here we show that constitutive deletion of the mGlu2 gene profoundly attenuates an effect of 5-HT2A receptor activation using the mouse head twitch response (HTR). MGlu2 and...
5-Hydroxytryptamine2A (5-HT2A) receptors are enriched in layers I and Va of the rat prefrontal cortex and neocortex and their activation increases the frequency of glutamatergic excitatory postsynaptic potentials/currents (EPSP/Cs) onto layer V pyramidal cells. A number of other G-protein coupled receptors (GPCRs) are also enriched in cortical layers I and Va and either induce (1-adrenergic...
PLoS One2011Jaymin Upadhyay, Scott J Baker, Prasant Chandran et al.
During wakefulness and in absence of performing tasks or sensory processing, the default-mode network (DMN), an intrinsic central nervous system (CNS) network, is in an active state. Non-human primate and human CNS imaging studies have identified the DMN in these two species. Clinical imaging studies have shown that the pattern of activity within the DMN is often modulated in various disease...
The serotonin (5-HT) hypothesis of schizophrenia arose from early studies on interactions between the hallucinogenic drug LSD (D-lysergic acid diethylamide) and 5-HT in peripheral systems. More recent studies have shown that the two major classes of psychedelic hallucinogens, the indoleamines (e.g., LSD) and phenethylamines (e.g. , mescaline), produce their central effects through a common...
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...
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...
The psychedelic hallucinogens are comprised of three different groups of compounds according to Ž . Ž . their chemical structure Fig. 1 : 1 the ergolines Ž which contain an indole moiety e.g. lysergic acid . Ž . diethylamide, LSD ; 2 simple indoleamine hallucinoŽ gens e.g. N,N-dimethyltryptamine, DMT and psilocy. bin which share an indoleamine structure with the Ž endogenous neurotransmitter...
The influence of 5-HT receptor agonists on the expression of BDNF in brain was determined. Administration of a hallucinogenic 5-HT2A /2C receptor agonist, but not a 5-HT1A receptor agonist, resulted in a significant but differential regulation of BDNF mRNA levels in hippocampus and neocortex. In the hippocampus, the 5-HT2A /2C receptor agonist significantly decreased BDNF mRNA expression in the...
Correlations between 5-hydroxytryptamine (5-HT) receptor binding affinities and human hallucinogenic potency have suggested that 5-HT2 receptors mediate the hallucinogenic effects of lysergic acid diethylamide (LSD) and phenethylamine hallucinogens. Electrophysiological studies have suggested that a subpopulation of gamma-aminobutyric acid (GABA)ergic interneurons in layer III of the rat...
The behavioral effect of single administration of +/- 3,4-methylene-dioxymethamphetamine (MDMA) on rats performing on the differential-reinforcement-of-low-rate 72-second schedule (DRL 72-sec) was compared before and after a period of repeated administration of MDMA known to deplete 5-hydroxytryptamine (5-HT) levels in the brain. Single administration of MDMA decreased reinforcement rate (1, 2,...