Oxytocin prevents cocaine-induced high-affect 50-kHz vocalizations in female rats.

Abstract

Cocaine's reinforcing properties are a key factor underlying the broad prevalence of cocaine use disorder. Few behavioral measures are capable of assessing cocaine-induced euphoria in murine models, limiting effective treatment options. However, positive affective states can be measured in rats by assessing the production of high-frequency, 50-kHz, vocalizations. Oxytocin (OXT) has been shown to attenuate cocaine-mediated behaviors in rodent models; however, the effect of OXT on cocaine-induced euphoria remains unknown. We addressed this by randomly assigning female rats to saline-saline, saline-cocaine, OXT-saline, or OXT-cocaine conditions and then assessing ultrasonic vocalizations. We found that saline-cocaine animals emitted a significantly higher percentage of 50-kHz calls relative to the other conditions, indicative of cocaine's euphoric effects. Notably, an OXT pretreatment prevented the cocaine-induced increase in high-affect calls. We also found that OXT significantly increased call duration in cocaine animals, inducing aversivelike call properties and further suggesting that OXT may attenuate positive affective states. There were minimal differences in call bandwidth across groups and no significant differences in call amplitude. When assessing the ultrasonic vocalization's qualitative features, we found that cocaine led to an increased production of flat and short call types, both of which are associated with positive states, which were not attenuated by OXT. Altogether, we found that cocaine administration successfully produced a high affective state in female rats. Moreover, an OXT pretreatment was sufficient to decrease the rewarding effects of cocaine administration and therefore may play a vital role in treating those suffering from cocaine use disorder. (PsycInfo Database Record (c) 2026 APA, all rights reserved).