Interrogating roles for VTA dopamine neurons in locomotion and ultrasonic vocalizations elicited by different classes of rewarding drugs.
Kate A Lawson, Stephen V Mahler
Psychopharmacology July 14, 2026 DOI: 10.1007/s00213-026-07125-5 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Observational study Peer reviewed |
|---|---|
| Sample size | 26 |
| Population | Male and female TH:cre rats and wildtype littermates |
| Interventions | Amphetamine Heroin Ketamine Saline |
| Dose | 2 mg/kg amphetamine, 0.25 mg/kg heroin, 30 mg/kg ketamine, 1 ml/kg saline |
| Duration | 1 hour tests |
| Topics | Ketamine |
| Keywords | Amphetamine Cno Dreadds Deepsqueak Heroin Hm3dq Hm4di |
| Key findings | Each drug had distinct effects on ultrasonic vocalizations and locomotion, and chemogenetic manipulations of ventral tegmental area dopamine neurons similarly suppressed amphetamine- or ketamine-induced locomotion and amphetamine-induced USVs. |
Abstract
In humans, researchers can readily query the subjective states elicited by drugs of abuse, but no such introspective readout is currently available in rodents. Rats can convey information relevant to their internal states via ultrasonic vocalizations (USVs). We sought to measure USVs and locomotor behavior as parallel behavioral indices of the effects of drugs and ventral tegmental area dopamine neuron (VTA DA) manipulations. In male and female TH: cre rats (n = 17) and wildtype littermates (n = 9), effects of IP amphetamine (2 mg/kg), heroin (0.25 mg/kg), ketamine (30 mg/kg), and saline (1 ml/kg) on USVs and locomotion were recorded in a series of 1 h tests. We also asked how chemogenetically inhibiting or exciting VTA DA impacted these behaviors. Each drug had distinct effects on USVs and locomotion, as did chemogenetic manipulations. Amphetamine elicited high-frequency (HF) USVs and increased locomotion, heroin elicited low-frequency USVs in some rats without altering HF-USVs or locomotion, and ketamine suppressed HF-USVs and transiently increased locomotion. VTA DA neuron inhibition suppressed HF-USVs and locomotion seen after saline, and DA stimulation increased locomotion but did not induce USV production. Surprisingly, both inhibiting and stimulating DA neurons appeared to similarly suppress amphetamine- or ketamine-induced locomotion, and amphetamine-induced USVs. These results confirm that USVs comprise a readout of certain effects of drugs and brain manipulations that cannot be attained by measuring locomotion alone. Potentially, USVs might therefore be useful for interrogating the subjective states of rats, and thus help bridge human and rodent neuroscience.
Comparable studies
Other preclinical and animal studies on ketamine, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| mTOR-Dependent Synapse Formation Underlies the Rapid Antidepressant Effects of NMDA Antagonists Rats | 2010 | Observational study | |
| Activation of Glutamatergic Neurotransmission by Ketamine: A Novel Step in the Pathway from NMDA Receptor Blockade to Dopaminergic and Cognitive Disruptions Associated with the Prefrontal Cortex Conscious rats | 1997 | Dose-response study with microdialysis and behavioral testing | |
| NMDAR inhibition-independent antidepressant actions of ketamine metabolites Mice | 2016 | Preclinical study | |
| The dissociative anaesthetics, ketamine and phencyclidine, selectively reduce excitation of central mammalian neurones by N‐methyl‐aspartate Spinal neurons in decerebrate or pentobarbitone-anaesthetized cats and rats | 1983 | Experimental study | |
| R-ketamine: a rapid-onset and sustained antidepressant without psychotomimetic side effects Mice | 2015 | Experimental study |