Interrogating roles for VTA dopamine neurons in locomotion and ultrasonic vocalizations elicited by different classes of rewarding drugs.

Rats can convey information about their internal states through ultrasonic vocalizations (USVs). In male and female TH:cre rats and wildtype littermates, amphetamine (2 mg/kg) elicited high-frequency USVs and increased locomotion, heroin (0.25 mg/kg) elicited low-frequency USVs in some rats without altering high-frequency USVs or locomotion, and ketamine (30 mg/kg) suppressed high-frequency USVs while transiently increasing locomotion. Chemogenetically inhibiting or stimulating ventral tegmental area dopamine neurons suppressed amphetamine- or ketamine-induced locomotion and amphetamine-induced USVs. USVs provide a behavioral readout of drug and brain manipulation effects that locomotion alone cannot capture, potentially helping bridge human and rodent neuroscience.

Study at a glance

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.