Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors

Delgado, Mercedes; Caicoya, Anne Gomez; Greciano, Virginia; Benhamú, Bellinda; López-Rodrı́guez, Marı́a L.; Fernández-Alfonso, Marı́a S.; Pozo, Miguel A.; Manzanares, Jorge; Fuentes, José A.

doi:10.1016/j.ejphar.2005.01.032

Cited by 22 publications

(17 citation statements)

References 30 publications

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“…Delgado (2005) shows that 5-HT 1 and 5-HT 3 receptors exert anxiolytic effects, which does correspond to some reports of DMT use. DMT is an agonist at 5-HT 2C receptors.…”

Section: Pharmacodynamicssupporting

confidence: 88%

Neuropharmacology of N,N-dimethyltryptamine

Carbonaro

Gatch

2016

Brain Research Bulletin

159

179

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N,N-Dimethyltryptamine (DMT) is an indole alkaloid widely found in plants and animals. It is best known for producing brief and intense psychedelic effects when ingested. Increasing evidence suggests that endogenous DMT plays important roles for a number of processes in the periphery and central nervous system, and may act as a neurotransmitter. This paper reviews the current literature of both the recreational use of DMT and its potential roles as an endogenous neurotransmitter. Pharmacokinetics, mechanisms of action in the periphery and central nervous system, clinical uses and adverse effects are also reviewed. DMT appears to have limited neurotoxicity and other adverse effects except for intense cardiovascular effects when administered intravenously in large doses. Because of its role in nervous system signaling, DMT may be a useful experimental tool in exploring how brain works, and may also be a useful clinical tool for treatment of anxiety and psychosis.

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“…Delgado (2005) shows that 5-HT 1 and 5-HT 3 receptors exert anxiolytic effects, which does correspond to some reports of DMT use. DMT is an agonist at 5-HT 2C receptors.…”

Section: Pharmacodynamicssupporting

confidence: 88%

Neuropharmacology of N,N-dimethyltryptamine

Carbonaro

Gatch

2016

Brain Research Bulletin

159

179

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“…We, however, could not see any significant amount of 5-HT2A positive cells in the same human nucleus as reported in animals (Freitas et al 2008). The function of both 5-HT receptor positive cells in this study may be involved with antinociception (Freitas et al 2008); their roles in behavior anxiety and depression have been illustrated by others (Delgado et al 2005;Lira et al 2003). 5-HT1A and 2A positive cells in the dorsal raphe might also control sleep and thus have an important relationship in depression (Ulak et al 2010).…”

Section: Discussionmentioning

confidence: 88%

Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals

Yeung

Kung

Yew

2010

AGE

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Serotonin receptor 1A and 2A positive cells in postmortem brainstems were demonstrated via immunohistochemistry in eight control age-matched elderly individuals and eight Alzheimer patients. The 5-HT1A positive cells were found in substantia nigra, pontile nucleus, and vagal as well as dorsal raphe nucleus, while 5-HT2A receptor positive cells were found in motor, sensory and spinal trigeminal nuclei, pontile nucleus, substantia nigra, and nucleus solitarius. A comparison in density of positive cells per unit area was made between control age-matched and Alzheimer individuals. Statistically significant differences (p ≤ 0.01) in density were observed in 5-HT1A cells in pontile, dorsal raphe, and vagal nuclei between control age-matched and Alzheimer, and in 5-HT2A positive cells in the sensory trigeminal nucleus, between control and Alzheimer. This de novo study indicated the presence of 5-HT1A and 5-HT2A receptor positive cells in the above nuclei of human brainstem and revealed differences in density between control age-matched and Alzheimer, indicating possible functional derangements in Alzheimer patients in these areas. In addition, colocalization studies indicated that 5-HT1A receptors were in cholinergic cells and gamma-aminobutyric acid positive fibers were linked to 5-HT2A receptor positive cells. It is hoped that understanding these two important 5-HT receptors and their localization might lead to advances in future therapeutic development.

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“…Consistent with this premise, Type I neurons co-expressed mRNA transcripts for the 5-HT 7 receptor, whereas Type IIC neurons and Type III neurons co-expressed transcripts for the 5-HT 2A receptor. Recent studies have suggested that activation of 5-HT 2A and 5-HT 7 receptors may facilitate anxiety-like behavior (Delgado et al, 2005, Hedlund, 2009), and that ligands with mixed 5-HT 1A receptor agonist and 5-HT 2A receptor antagonist properties may make more effective anxiolytics (Delgado et al, 2005). …”

Section: Discussionmentioning

confidence: 99%

“…Notably, the Type IIA neurons expressed transcripts for the 5-HT 3 and 5-HT 7 receptor subtypes, whereas the subpopulation of Type III neurons lacking 5-HT 1A receptor transcripts expressed transcripts for the 5-HT 3 and 5-HT 2C receptor subtypes suggesting that this population of neurons could respond to local 5-HT release with a rapid excitation mediated by 5-HT 3 receptor activation (Farber et al, 2004) as well as a slower excitation mediated by 5-HT 2C/7 receptor activation (Guo et al, 2009). Like activation of 5-HT 7 receptors, activation of 5-HT 2C and 5-HT 3 receptors has been reported to have anxiogenic-like actions (Delgado et al, 2005, Harada et al, 2006, Dekeyne et al, 2008) suggesting that these neurons may play a role in the rapid anxiogenic response to acute stressors. However, a caveat to this hypothesis is that the BNST ALG is primarily a GABAergic system and it is possible that a subset of these neurons act as local circuit inhibitory interneurons, and function to inhibit the activity of BNST ALG output neurons.…”

Section: Discussionmentioning

confidence: 99%

Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

et al. 2012

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The bed nucleus of the stria terminalis (BNST) plays a critical role in regulating the behavioral response to stress. Stressors that activate the BNST also activate serotonergic (5-HT) systems. Hence, maladaptive changes of 5-HT receptor expression may contribute to stress-induced anxiety disorders. The BNST contains three neuronal types, Type I – III neurons. However, little is known about 5-HT receptor subtypes mRNA expression in these neurons, or whether it can be modulated by stress. Whole-cell patch clamp recording from Type I – III neurons was used in conjunction with single cell RT-PCR to characterize 5-HT receptor mRNA expression, and examine the effects of stress on this expression. We report that Type I neurons expressed mRNA transcripts predominantly for 5-HT1A and 5-HT7 receptors. Type II neurons expressed transcripts for every 5-HT receptor except the 5-HT2C receptor. Type II neurons were divided into three sub-populations: Type IIA in which transcripts for 5-HT3 and 5-HT7 receptors predominate, Type IIB that mainly express 5-HT1B and 5-HT4 receptor transcripts, and Type IIC in which transcripts for 5-HT1A and 5-HT2A receptors predominate. Type III neurons were also subdivided into two sub-populations; one that predominantly expressed transcripts for 5-HT1A, 5-HT1B and 5-HT2A receptors, and another that mainly expressed transcripts for 5-HT2C receptor. Unpredictable shock stress (USS) caused a long-lasting increase in anxiety-like behavior, and a concomitant decrease in 5-HT1A transcript expression in Type I – III neurons, as well as an up-regulation of a transcriptional repressor of 5-HT1A gene expression, deformed epidermal autoregulatory factor 1(Deaf-1). Significantly USS decreased 5-HT1A protein level, and increased the level of Deaf-1. USS also increased 5-HT1B transcript expression in Type III neurons, as well as 5-HT7 expression in Type I and II neurons. These data suggest that cell type-specific disruption of 5-HT receptor expression in BNSTALG neurons may contribute to stress-induced anxiety disorders.

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Anxiolytic-like effect of a serotonergic ligand with high affinity for 5-HT1A, 5-HT2A and 5-HT3 receptors

Cited by 22 publications

References 30 publications

Neuropharmacology of N,N-dimethyltryptamine

Neuropharmacology of N,N-dimethyltryptamine

Localization of 5-HT1A and 5-HT2A positive cells in the brainstems of control age-matched and Alzheimer individuals

Differential distribution of serotonin receptor subtypes in BNSTALG neurons: Modulation by unpredictable shock stress

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