Ultrasonic vocalization reveals individual differences in the rewarding and motivational effects of amphetamine in rats
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The pleasurable and euphoric effects of drugs play an important role in drug abuse; however, there are no established preclinical models for directly assessing the hedonic effects of drugs in rodents. The purpose of this dissertation was to investigate rat ultrasonic vocalizations (USVs) as a potential method for measuring positive affective states associated with amphetamine reinforcement. USVs are high-frequency social signals that rats use to communicate with one another. Calls in the 50-kHz range are thought to be a sign of positive affect, since they are elicited by naturally rewarding stimuli, and are modulated by mesolimbic dopamine activity. At the time this dissertation was begun, the majority of USV research focused on natural rewards, such as sex and social interactions, and the USVs associated with repeated exposure to a drug or appetitive desire for a drug had not been studied. Therefore, the objective of this dissertation was to characterize the production of 50-kHz USVs during repeated administration of amphetamine within different paradigms commonly used to study the behavioral and motivational effects of stimulants in rats. First, I found that the 50-kHz USVs elicited by amphetamine were sensitized by repeated exposure, showing that USV expression parallels the sensitization of mesolimbic circuitry that is involved in the development of addiction. Second, I found that rats produce conditioned anticipatory 50-kHz USVs during exposure to cues that predicted amphetamine, with the magnitude of anticipatory calling increasing as drug-cue associations were learned and strengthened. Third, I found that the number of unconditioned 50-kHz USVs produced during the initial amphetamine exposure predicted the subsequent expression of anticipatory 50-kHz USVs, the development of conditioned place preference for an amphetamine-paired environment, and corticosterone responses to the drug. Overall, these findings suggest that 50-kHz USVs are an expression of behavioral arousal associated with both the positive effects of amphetamine itself, and the incentive-motivational states elicited by drug-paired cues. In addition, they show that the intensity of the initial 50-kHz USV response to amphetamine reflects individual differences in sensitivity to drug reinforcement.