Pharmacological characterization of 50-kHz ultrasonic vocalizations in rats: Comparison of the effects of different psychoactive drugs and relevance in drug-induced reward

Significant evidence suggests that ultrasonic vocalizations (USVs) may index the emotional state in rats, and 50-kHz USVs have been proposed as a tool to investigate the rewarding properties of drugs. Apart from the evidence on some psychostimulants, little is known about the effects of other drugs with rewarding properties on emission of 50-kHz USVs. To further elucidate the neuropharmacology of 50-kHz USVs and their relevance in drug-induced reward, this study characterized the effects of different drugs possessing rewarding properties on 50-kHz USVs in adult male rats. Rats received the acute administration of 3,4-methylenedioxymethamphetamine (MDMA, 5–15 mg/kg, i.p.), methylphenidate (2.5–10 mg/kg, i.p.), morphine (1–5 mg/kg, s.c.), or nicotine (0.1–0.4 mg/kg, s.c.). The number and acoustic features of 50-kHz USVs and their subtypes were then measured. As a comparison, additional rats received the acute administration of amphetamine (2 mg/kg, i.p.), which strongly stimulates the emission of 50-kHz USVs. Methylphenidate, similar to amphetamine, increased the total number of 50-kHz USVs emitted by rats, and also modified their acoustic features. Conversely, MDMA, morphine, and nicotine did not elevate the total number of 50-kHz USVs. However, these drugs modified the acoustic features of 50-kHz USVs, as well as the number and acoustic features of specific subtypes of vocalizations. This study demonstrates that major differences exist in the effects of psychoactive drugs on 50-kHz USVs in rats. These findings provide a better understanding of psychoactive properties of drugs with rewarding properties and usefulness of 50-kHz USVs in assessment of these properties.

► Psychoactive drugs with rewarding properties have different effects on the emission and acoustic features of 50-kHz USVs.
► Dopaminergic psychostimulants are most effective in stimulating 50-kHz USVs.
► The evaluation of 50-kHz USVs may be useful in the study of the mechanisms of action of drugs.