Enhanced effect of the hallucinogen DOI in L-DOPA receptor Gpr143-deficient mice.
Daiki Masukawa, Rei Tajika, Yoshimi Ichimaru, Masaaki Kurihara, Tsutomu Suzuki, Yoshio Goshima
Journal of Pharmacological Sciences June 1, 2026 DOI: 10.1016/j.jphs.2026.04.002 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Experimental study Peer reviewed |
|---|---|
| Population | Mice and Chinese hamster ovary cells |
| Interventions | 2 5-dimethoxy-4-iodoamphetamine (DOI) |
| Topics | Serotonin |
| Keywords | 2,5-dimethoxy-4-iodoamphetamine Gpr143 |
| Key findings | GPR143 negatively regulates 5-HT2A receptor signaling and attenuates behavioral responses to hallucinogens. |
Abstract
Hallucinogens, such as lysergic acid diethylamide, act primarily through the 5-hydroxytryptamine 2A (5-HT2A) receptor, but their regulatory mechanisms remain unclear. G protein-coupled receptor 143 (GPR143), an L-3,4-dihydroxyphenylalanine (L-DOPA) receptor, modulates specific GPCRs. We examined the role of GPR143 in the action of 5-HT2A receptor agonist 2,5-dimethoxy-4-iodoamphetamine (DOI). DOI-induced hyperlocomotion and c-Fos expression in the nucleus accumbens were enhanced in GPR143 knockout mice. In Chinese hamster ovary cells expressing 5-HT2A receptor, DOI-induced extracellular signal-regulated kinase phosphorylation was suppressed by co-expression of GPR143. These findings suggest that GPR143 negatively regulates 5-HT2A receptor signaling and attenuates behavioral responses to hallucinogens.
Comparable studies
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| 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 8
- Hallucinogens and Serotonin 5-HT2A Receptor-Mediated Signaling Pathways Current Topics in Behavioral Neurosciences 2017
- DOI-Induced Activation of the Cortex: Dependence on 5-HT2AHeteroceptors on Thalamocortical Glutamatergic Neurons Journal of Neuroscience December 1, 2000
- Novel Psychoactive Substances—Recent Progress on Neuropharmacological Mechanisms of Action for Selected Drugs Frontiers in Psychiatry August 18, 2017
- Hallucinogenic/psychedelic 5HT2A receptor agonists as rapid antidepressant therapeutics: Evidence and mechanisms of action Journal of Psychopharmacology March 19, 2021
- Possible Involvement of Hallucinogenic Effects in the Aversive Effects Induced by Kappa‐Opioid and 5‐ HT 2A / 2C Receptor Agonists in Mice Neuropsychopharmacology Reports November 23, 2025
and 3 more in the library