Neuropharmacological and behavioral characterization of 3F-phenetrazine, a novel amphetamine-like substance, in male mice and rats.
Sumin Ban, Kyung Oh Jeon, Su Yeon Seo, Young Ju Do, Choon-Gon Jang, Han Young Eom, Kee Kwang Kim, Hye Jin Cha, Eun Young Jang
European Journal of Pharmacology August 18, 2026 DOI: 10.1016/j.ejphar.2026.179253 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Preclinical behavioral and neurochemical study in rodents Peer reviewed |
|---|---|
| Population | Male mice and rats |
| Intervention | 3F-phenetrazine |
| Measures | open-field test, conditioned place preference, self-administration test |
| Topics | Serotonin |
| Keywords | 3f-phenetrazine Abuse potential Addiction-like behaviors Dorsal striatum Nucleus accumbens |
| Key points | 3F-phenetrazine produced psychostimulant, rewarding, and reinforcing effects in male rodents: acute administration increased locomotor activity, repeated administration induced behavioral sensitization, and the drug supported conditioned place preference and self-administration. It also increased serotonin levels, c-Fos and Arc expression, and dendritic spine density in the dorsal striatum and/or nucleus accumbens, which the authors interpret as evidence of serotonergic neurotransmission and addiction-related neuroplasticity underlying high abuse liability. |
Abstract
3-Fluorophenetrazine (3F-phenetrazine) is a novel amphetamine-like substance that is structurally similar to phenmetrazine and 3F-phenmetrazine. Despite the emergence of 3F-phenetrazine in recreational drug markets, its neuropharmacological profile and abuse liability remain poorly characterized. This study is the first to investigate the psychostimulant, rewarding, and reinforcing properties of 3F-phenetrazine in male rodents using open-field test, conditioned place preference, and self-administration tests. In addition to the behavioral assessments, we analyzed serotonin levels, c-Fos and activity-regulated cytoskeleton-associated protein (Arc) expression, and dendritic spine density in the dorsal striatum and nucleus accumbens following acute or repeated 3F-phenetrazine administration in mice. Body weight changes during 3F-phenetrazine treatment and withdrawal periods were also evaluated in normal mice. Acute 3F-phenetrazine administration significantly increased locomotor activity, whereas repeated 3F-phenetrazine administration induced behavioral sensitization in mice. In the conditioned place preference and self-administration studies, 3F-phenetrazine produced a significant drug-paired place preference in mice and supported self-administration in rats, confirming its potent rewarding and reinforcing properties. Neurochemical analysis revealed that 3F-phenetrazine administration increased serotonin levels, c-Fos and Arc expression, and dendritic spine density in the dorsal striatum and/or nucleus accumbens, indicating that acute neurochemical alteration and addiction-related neuroplasticity occurred after repeated administration. Finally, 3F-phenetrazine treatment did not affect body weight. Collectively, these findings demonstrate that 3F-phenetrazine exerts significant psychostimulant, rewarding, and reinforcing effects via serotonergic neurotransmission and addiction-related neuroplastic changes in the dorsal striatum and/or nucleus accumbens. This study provides critical scientific evidence for the high abuse liability of 3F-phenetrazine, underscoring the need for legal regulation of its nonmedical use.
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
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