Inter-individual diversity and intra-individual stability of amphetamine-induced sensitization of frequency-modulated 50-kHz vocalization in Sprague–Dawley rats

Abstract

RationalePropensity for drug dependence shows great diversity that is related to intrinsic neurobiological factors. This diversity is important both for the understanding of these traits and for the development of therapies.ObjectivesThe goals of the study were (1) to define, using ultrasonic vocalization characteristics, inter-individual differences in rats’ propensity for sensitization to amphetamine, (2) to test whether possible resistance to this effect could be overcome with repetitive treatment, and (3) to seek useful predictors of the propensity.MethodsRats were subject to tests meant to characterize their anxiety, pain sensitivity, and responses to novelty and natural rewards. Then they were subject to the so-called two-injection protocol of sensitization (using amphetamine) followed by 2 weeks of daily amphetamine treatment, 2-week withdrawal, and final amphetamine challenge. The development and outcome of sensitization were monitored by measuring 50-kHz vocalization.ResultsThe two-injection protocol yielded three patterns of changes in the frequency-modulated 50-kHz vocalization response to amphetamine. These patterns persisted after completion of the extended drug treatment. Rats with lower sensitivity to pain or with longer latency of their vocalization response to the first drug exposure showed an increased propensity for ultrasonic vocalization sensitization.ConclusionVulnerability to sensitization of frequency-modulated 50-kHz vocalization response of Sprague–Dawley rats to amphetamine, which supposedly reflects rats’ propensity for amphetamine dependence, shows large inter-individual diversity. Resistance to this effect, which is evident in a majority of the rats, cannot be overcome even with prolonged intermittent drug treatment under the conditions (novelty) that promote sensitization.

Voluntary ethanol consumption changes anticipatory ultrasonic vocalizations but not novelty response

“…Future research should focus on understanding USVs subtypes in response to both conditioned and unconditioned reward. The large body of evidence supports our hypothesis that rodent USVs are reliable [21], and capable of elucidating these separate reward systems (wanting and liking) [47–49]. For example, in a conditioned place preference experiment, conditioned place preference magnitude is positively correlated with 50 kHz USVs in the drug paired side [27,30].…”

“…USVs show large individual differences across rats but remain stable across time, indicating they can be used to study trait-like characteristics in affective and motivational states in rodents [21,22]. Fifty kHz USVs are emitted in response to appetitive stimuli and are indicative of positive affect [23–27].…”

“…To determine how these individual difference traits change, we measured the IEN response and USV response before and after the intermittent ETOH exposure phase. Since 50 kHz USVs are a reliable measure of rodent positive affect [21,26,39,40], we designed the USV test to probe for 50 kHz USVs because our objective was to determine how the response to naturally rewarding stimulation changes after ETOH drinking. We hypothesized that rats would decrease their locomotor activity in the IEN test after ETOH exposure.…”

A rodent “self-report” measure of methamphetamine craving? Rat ultrasonic vocalizations during methamphetamine self-administration, extinction, and reinstatement

“…However, there is evidence that “50kHz” USVs varying little in frequency over time (flats), and those characterized by frequency modulation over time (either with or without a rapidly oscillating “trill” pattern) are differentially produced based upon behavioral context and due to experimental manipulations. For example, administration of psychostimulant drugs preferentially elicits trills and other non-trill frequency-modulated vocalizations (FMs), production of which sensitize with repeated drug administration [33, 36–39], and they have been proposed to reflect positive affective states [27, 28]. FMs and trills are also emitted preferentially in “sign tracking” animals during a cocaine conditioned place preference task, and therefore may reflect incentive salience of rewards and their cues [40].…”

Sexual performance and precontact 50-kHz ultrasonic vocalizations in WAG/Rij rats: Effects of opioid receptor treatment

“…Recently, more data have supported the hypothesis that ultrasonic vocalizations in rats serve a communication function [11][12][13][14][15]. Parallel to the communicational role, ultrasonic vocalizations at the 50-kHz band in rats can be an indicator of a positive emotional state which relates to the dopamine level, mu opioid receptor stimulation in the ventral tegmental area, and self-and drug-stimulation of the rewarding systems [16][17][18][19][20][21]. It has been observed that 50-kHz vocalizations also occur in situations not pleasant for rats such as fights or when the rats are in an open-field apparatus [6,22].…”