Positive affective vocalizations during cocaine and sucrose self-administration: a model for spontaneous drug desire in rats.

Ultrasonic vocalizations in the 50 kHz range (50 kHz USVs) are emitted by rodents upon activation of positive affective states and appear to be a direct measure of internal emotional and motivational urges to seek rewarding stimuli such as drugs of abuse. Since these behavioral responses do not rely on training for expression, they can be viewed as a "spontaneous" measure of affective state. The goal of the present study was to monitor spontaneous USVs throughout a widely-used cocaine self-administration and reinstatement model of addiction and relapse. To gain insight into the changes in affective state across the different phases of a standard self-administration experiment, we measured 50 kHz USVs in rats during cocaine self-administration and reinstatement, and compared these to sucrose self-administration and reinstatement. During cocaine self-administration, the number of 50 kHz USVs increased over acquisition of self-administration and decreased during extinction. Furthermore, the number of USVs on the first day of acquisition in the cocaine experiment was positively correlated with how rapidly cocaine self-administration was acquired. These findings suggest that the initial affective response to cocaine may be a sensitive predictor of the motivational efficacy of rewarding stimuli and therefore the susceptibility to acquire self-administration of cocaine. Cue- and cocaine-induced reinstatement elevated 50 kHz USVs above extinction levels. Rats trained for sucrose self-administration showed no elevation in USVs during acquisition when USVs were considered over the entire 2 h session, but they did show an elevation in USVs during acquisition when considered over only the first 5 min of the session. As with cocaine-induced reinstatement, sucrose-induced reinstatement produced significantly more USVs compared to the prior extinction day. Taken together, USVs may serve as a sensitive and dynamic non-invasive measure that spontaneously (i.e. without any formal reinforcement contingencies) quantifies the extent to which positive affect is elicited by rewards such as drugs of abuse.