Dextromethorphan moderates reward deficiency associated with central serotonin transporter availability in 3,4-methylenedioxy-methamphetamine-treated animals.
Chuang-Hsin Chiu, Kuo-Hsing Ma, Eagle Yi-Kung Huang, Hsien-Wen Chang, Shao-Ju Weng, Tsung-Hsun Yu, Shiou-Shiow Farn, Yu-Yeh Kuo, Wen-Sheng Huang, Cheng-Yi Cheng, Pao-Luh Tao, Skye Hsin-Hsien Yeh
Journal of the Chinese Medical Association : JCMA May 1, 2024 DOI: 10.1097/JCMA.0000000000001087 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Animal study Longitudinal Peer reviewed |
|---|---|
| Population | Rats |
| Interventions | MDMA Dextromethorphan |
| Duration | 14 days |
| Topics | Serotonin |
| Keywords | Addiction research Drug interactions Harm reduction Brain chemistry |
| Citations | 4 |
| Key points | Dextromethorphan co-administration reversed MDMA-induced loss of serotonin transporters in rats, restoring SERT binding by approximately 23% after 14 days. |
Abstract
The neurotoxicity of 3,4-methylenedioxy-methamphetamine (MDMA) to the serotonergic system is well-documented. Dextromethorphan (DM), an antitussive drug, decreased morphine- or methamphetamine (MA)-induced reward in rats and may prevent MDMA-induced serotonergic deficiency in primates, as indicated by increased serotonin transporter (SERT) availability. We aimed to investigate the effects of DM on reward, behavioral sensitization, and neurotoxicity associated with loss of SERT induced by chronic MDMA administration in rats. Conditioned place preference (CPP) and locomotor activity tests were used to evaluate drug-induced reward and behavioral sensitization; 4-[ 18 F]-ADAM/animal-PET and immunohistochemistry were used to explore the effects of DM on MDMA-induced loss of SERT. MDMA significantly reduced SERT binding in the rat brain; however, co-administration of DM significantly restored SERT, enhancing the recovery rate at day 14 by an average of ~23% compared to the MDMA group. In confirmation of the PET findings, immunochemistry revealed MDMA reduced SERT immunoactivity in all brain regions, whereas DM markedly increased the serotonergic fiber density after MDMA induction. Behavioral tests and in vivo longitudinal PET imaging demonstrated the CPP indexes and locomotor activities of the reward system correlate negatively with PET 4-[ 18 F]ADAM SERT activity in the reward system. Our findings suggest MDMA induces functional abnormalities in a network of brain regions important to decision-making processes and the motivation circuit. DM may exert neuroprotective effects to reverse MDMA-induced neurotoxicity.
Comparable studies
Other preclinical and animal studies on serotonin, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Psilocybin induces rapid and persistent growth of dendritic spines in frontal cortex in vivo Mice | 2021 | Observational cohort | |
| Neurotoxicity of the psychedelic amphetamine, methylenedioxymethamphetamine. Rats (implied by typical neurochemical study context) | 1987 | Experimental study | |
| Psychedelics promote neuroplasticity through the activation of intracellular 5-HT2A receptors In vitro and in vivo (rodent) models | 2023 | Experimental study | |
| 3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of [3H]paroxetine-labeled serotonin uptake sites. Rat brain | 1987 | Animal experiment | |
| Comparison of the monoamine transporters from human and mouse in their sensitivities to psychostimulant drugs Human and mouse dopamine, norepinephrine, and serotonin transporters expressed in cells | 2006 | In vitro laboratory study |
Citations in the library
Cites 13
- Altered Serotonin Innervation Patterns in the Forebrain of Monkeys Treated with (±)3,4-Methylenedioxymethamphetamine Seven Years Previously: Factors Influencing Abnormal Recovery Journal of Neuroscience June 15, 1999
- Reducedin vivobinding to the serotonin transporter in the cerebral cortex of MDMA (‘ecstasy’) users The British Journal of Psychiatry July 1, 1999
- Involvement of 5-HT2A receptors in MDMA reinforcement and cue-induced reinstatement of MDMA-seeking behaviour The International Journal of Neuropsychopharmacology October 14, 2010
- Sensitization to MDMA locomotor effects and changes in the functionality of 5-HT2A and D2 receptors in mice Behavioural Pharmacology June 29, 2011
- Amitriptyline Accelerates SERT Binding Recovery in a Rat 3,4-Methylenedioxymethamphetamine (MDMA) Model: In Vivo 4-[18F]-ADAM PET Imaging International Journal of Molecular Sciences June 24, 2022
and 8 more in the library