AI Article Synopsis
Article Abstract
The amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) reverses dopamine and serotonin transporters to produce efflux of dopamine and serotonin, respectively, in regions of the brain that have been implicated in reward. However, the role of serotonin/dopamine interactions in the behavioral effects of MDMA remains unclear. We previously showed that MDMA-induced locomotion, serotonin and dopamine release are 5-HT(2B) receptor-dependent. The aim of the present study was to determine the contribution of serotonin and 5-HT(2B) receptors to the reinforcing properties of MDMA.We show here that 5-HT(2B) (-/-) mice do not exhibit behavioral sensitization or conditioned place preference following MDMA (10 mg/kg) injections. In addition, MDMA-induced reinstatement of conditioned place preference after extinction and locomotor sensitization development are each abolished by a 5-HT(2B) receptor antagonist (RS127445) in wild type mice. Accordingly, MDMA-induced dopamine D1 receptor-dependent phosphorylation of extracellular regulated kinase in nucleus accumbens is abolished in mice lacking functional 5-HT(2B) receptors. Nevertheless, high doses (30 mg/kg) of MDMA induce dopamine-dependent but serotonin and 5-HT(2B) receptor-independent behavioral effects.These results underpin the importance of 5-HT(2B) receptors in the reinforcing properties of MDMA and illustrate the importance of dose-dependent effects of MDMA on serotonin/dopamine interactions.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2775951 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0007952 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Potent and Selective Human 5-HT Serotonin Receptor Antagonists: 4'-Cyano-(N)-methanocarba-adenosines by Synthetic Serendipity.
J Med Chem
December 2024
Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institutes of Health, Bethesda, Maryland 20892, United States.
Rigidified nucleoside derivatives with (N)-methanocarba replacement of ribose have been repurposed as peripheral subtype-selective 5-HT serotonin receptor antagonists for heart and lung fibrosis and intestinal/vascular conditions. 4'-Cyano derivative (MRS8209; , 4.27 nM) was 47-fold (human binding, but not rat and mouse) and 724-fold (functionally) selective at 5-HTR, compared to antitarget 5-HTR, and predicted to form a stable receptor complex using docking and molecular dynamics.
View Article and Find Full Text PDFMescaline-induced behavioral alterations are mediated by 5-HT2A and 5-HT2C receptors in rats.
Pharmacol Biochem Behav
December 2024
Psychedelic Research Centre, National Institute of Mental Health, Topolová 748, Klecany 250 67, Czechia. Electronic address:
Rationale: Mescaline is a classical psychedelic compound with a phenylethylamine structure that primarily acts on serotonin 5-HT2A/C receptors, but also binds to 5-HT1A and 5-HT2B receptors. Despite being the first psychedelic ever isolated and synthesized, the precise role of different serotonin receptor subtypes in its behavioral pharmacology is not fully understood.
Objectives: In this study, we aimed to investigate how selective antagonists of 5-HT2A, 5-HT2B, 5-HT2C, and 5-HT1A receptors affect the behavioral changes induced by subcutaneous administration of mescaline (at doses of 10, 20, and 100 mg/kg) in rats.
Serotonin acts through multiple cellular targets during an olfactory critical period.
iScience
November 2024
Departments of Biology and Neuroscience, West Virginia University, Morgantown, WV 26505, USA.
Serotonin (5-HT) modulates early development during critical periods when experience drives heightened levels of plasticity in neurons. Here, we investigate the cellular mechanisms by which 5-HT modulates critical period plasticity (CPP) in the olfactory system of . We first demonstrate that 5-HT is necessary for experience-dependent structural plasticity in response to chronic CO exposure and can re-open the critical period long after it normally closes.
View Article and Find Full Text PDFThe periaxonal space as a conduit for cerebrospinal fluid flow to peripheral organs.
Proc Natl Acad Sci U S A
November 2024
Department of Forensic Analytical Toxicology, School of Forensic Medicine, China Medical University, Shenyang 110122, China.
Mechanisms controlling the movement of the cerebrospinal fluid (CSF) toward peripheral nerves are poorly characterized. We found that, in addition to the foramina Magendie and Luschka for CSF flow toward the subarachnoid space and glymphatic system, CSF outflow could also occur along periaxonal spaces (termed "PAS pathway") from the spinal cord to peripheral organs, such as the liver and pancreas. When interrogating the latter route, we found that serotonin, acting through 5-HT receptors expressed in ependymocytes that line the central canal, triggered Ca signals to induce polymerization of F-actin, a cytoskeletal protein, to reduce the volume of ependymal cells.
View Article and Find Full Text PDFSerotonin-2B receptor (5-HTR) expression and binding in the brain of APP/PS1 transgenic mice and in Alzheimer's disease brain tissue.
Neurosci Lett
January 2025
Department of Neurobiology, Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark; Department of Life Sciences, School of Sciences, European University Cyprus, Nicosia, Cyprus. Electronic address:
Despite well-documented dysregulation in central serotonergic signaling in Alzheimer's disease (AD), knowledge about the potential involvement of the serotonin-2B receptor (5-HTR) subtype remains sparse. Here, we assessed the levels of 5-HTRs in brain tissue from APP/PS1 transgenic (TG) mice, AD patients, and adult microglial cells. 5-HTR mRNA was measured by RT-qPCR in ageing TG and wild-type (WT) mice, in samples from the middle frontal gyrus of female, AD and control subjects, and in microglia from the cerebral cortex of WT mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!