Serotonergic psychedelics and amphetamine shift male rat ultrasonic vocalizations toward call patterns associated with positively valenced states.
Ewelina Cyrano, Joanna Gołębiowska, Piotr Popik, Paweł Zajdel, Agnieszka Potasiewicz
Progress in Neuro-Psychopharmacology and Biological Psychiatry September 18, 2026 DOI: 10.1016/j.pnpbp.2026.111940 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Population | Male Wistar rats |
| Interventions | DOI LSD lisuride amphetamine |
| Dose | DOI 1.25-2.5 mg/kg; LSD 0.04-0.08 mg/kg; lisuride 0.03 or 0.3 mg/kg; amphetamine 1 mg/kg |
| Measures | DeepSqueak, DeepLabCut, SimBA, head-twitch response (HTR) |
| Topics | Serotonin |
| Keywords | Affective vocalization Behavioral phenotyping Machine learning Rodent |
| Key findings | DOI (2.5 mg/kg) and LSD (0.08 mg/kg), but not lisuride or amphetamine, induced head-twitch responses, while only amphetamine increased activity. Total ultrasonic vocalizations increased after amphetamine and both DOI doses, but cluster analyses indicated the compounds altered the vocal repertoire rather than simply increasing overall calling. The authors suggest these compounds may shift vocal patterns toward those associated with positively valenced states, and that vocal profiles should be viewed as a complementary affective readout rather than a substitute marker of psychedelic-like activity. |
Abstract
Psychedelics and psychostimulants produce subjective and often positive affective effects in humans. In rats, positive affective states are often associated with frequency-modulated ultrasonic vocalizations (USVs). We examined whether the hallucinogenic 2,5-dimethoxy-4-iodoamphetamine (DOI; 1.25-2.5 mg/kg) and LSD (0.04-0.08 mg/kg), the non-hallucinogenic lisuride (0.03 or 0.3 mg/kg) and the psychostimulant amphetamine (1 mg/kg) modulate USV emission, activity, and head-twitch response (HTR) in male Wistar rats. USVs were detected using DeepSqueak and clustered in a custom, unsupervised manner using variational autoencoder-based, and frequency-based embeddings. Behavior was analyzed using DeepLabCut and SimBA AI/machine learning tools. DOI (2.5 mg/kg) and LSD (0.08 mg/kg), but not lisuride or amphetamine induced HTR, whereas only amphetamine (1 mg/kg) increased activity. DeepSqueak detected nearly 48,000 calls, and UMAP-based k-means clustering identified four broad call categories: 22-kHz alarm and 50-kHz flat, step-up/trill, and upward-ramp-like calls. Total call emission increased after amphetamine and both DOI doses. However, cluster-based analyses indicated that the compounds did not merely increase overall calling but altered the vocal repertoire. DOI and LSD (0.04 mg/kg) reduced occupancy of the flat-call cluster, a call type typically unrelated to reward or appetitive behavior. In contrast, LSD (0.08 mg/kg), lisuride (0.03 mg/kg), and amphetamine increased occupancy of frequency-modulated clusters, call categories often associated with positive affect. Serotonergic psychedelics, lisuride, and amphetamine alter rat ultrasonic vocalizations and may shift vocal repertoires toward patterns associated with positively valenced states. USV profiles did not parallel HTR and should be viewed as a complementary affective readout rather than a substitute marker of psychedelic-like activity.
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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and 13 more in the library