Ultrasonic Vocalizations as a Measure of Affect in Preclinical Models of Drug Abuse: A Review of Current Findings

Abstract

The present review describes ways in which ultrasonic vocalizations (USVs) have been used in studies of substance abuse. Accordingly, studies are reviewed which demonstrate roles for affective processing in response to the presentation of drug-related cues, experimenter- and self-administered drug, drug withdrawal, and during tests of relapse/reinstatement. The review focuses on data collected from studies using cocaine and amphetamine, where a large body of evidence has been collected. Data suggest that USVs capture animals’ initial positive reactions to psychostimulant administration and are capable of identifying individual differences in affective responding. Moreover, USVs have been used to demonstrate that positive affect becomes sensitized to psychostimulants over acute exposure before eventually exhibiting signs of tolerance. In the drug-dependent animal, a mixture of USVs suggesting positive and negative affect is observed, illustrating mixed responses to psychostimulants. This mixture is predominantly characterized by an initial bout of positive affect followed by an opponent negative emotional state, mirroring affective responses observed in human addicts. During drug withdrawal, USVs demonstrate the presence of negative affective withdrawal symptoms. Finally, it has been shown that drug-paired cues produce a learned, positive anticipatory response during training, and that presentation of drug-paired cues following abstinence produces both positive affect and reinstatement behavior. Thus, USVs are a useful tool for obtaining an objective measurement of affective states in animal models of substance abuse and can increase the information extracted from drug administration studies. USVs enable detection of subtle differences in a behavioral response that might otherwise be missed using traditional measures.

Role of hypocretin/orexin receptor blockade on drug-taking and ultrasonic vocalizations (USVs) associated with low-effort self-administration of cathinone-derived 3,4-methylenedioxypyrovalerone (MDPV) in rats

“…We observed that suvorexant attenuated 50-kHz USVs during each of pre- and post-lever time-points. Our prior work shows that suvorexant pretreatment suppresses cocaine-evoked elevations in ventral striatal dopamine (Gentile et al 2017) which supports the hypothesis that mesolimbic dopamine underlies the elicitation of 50-kHz USVs (for reviews, see Barker et al 2015; Brudzynski 2015). From the three categories of call types analyzed in the present report, 50-kHz USV call type remained stable irrespective of suvorexant pre-treatment with majority of calls belonging to FM 1–2 call type which supports earlier work describing USVs associated with cocaine-paired cue presentation (Meyer et al 2012).…”

Comparing rewarding and reinforcing properties between ‘bath salt’ 3,4‐methylenedioxypyrovalerone (MDPV) and cocaine using ultrasonic vocalizations in rats

“…Positive and negative affective states can be non-invasively probed in rats by recordings ultrasonic vocalizations (USVs); rewarding stimuli evoke 50-kHz USVs whereas aversive stimuli evoke 22-kHz USVs (e.g., Blanchard et al , 1991; Sanchez, 1993; Brudzynski and Pniak, 2002). In models of substance use disorders, 50-kHz USVs consistently associate with systemic- and self-administration of cocaine and amphetamine whereas 22-kHz USVs associate with corresponding drug withdrawal states (e.g., Barros and Miczek, 1996; Wintink and Brudzynski, 2001; Barker et al , 2010; for review, see Barker et al , 2015). Production of positive 50-kHz USVs are supported by mesolimbic dopamine (DA) transmission, as direct infusion of amphetamine into the nucleus accumbens (NAcc), a principal target structure of DA-producing neuronal afferents from ventral tegmental area (VTA), readily evokes 50-kHz USVs (Burgdorf et al , 2001; Thompson et al , 2006).…”

Subthalamic nucleus mediates the modulation on cocaine self-administration induced by ultrasonic 3 vocalizations playback in rats

“…Moreover, our data obtained with the CPP (a classical and well established paradigm to study the rewarding properties of drug and non-drug stimuli; see Tzschentke 2007 for a review), showed that rats, during the test day, kept approaching the compartment associated with the USV in absence of their playback. Considering the 50-kHz USV are uttered during – mostly positive – various social interactions (Burgdorf et al 2008), but also after exposure to food and drugs (Browning et al 2011; Barker, Simmons, & West 2015), or in mildly aversive situations as a short social isolation (Wöhr et al 2007), we can reasonably suppose that the social and rewarding aspects of the 50-kHz USV could overlap in some circumstances, while in other situations one aspect could prevail on the other. Further research is necessary to investigate this point.…”

“…This acoustic communication could thus play an important role in the effects mediated by the peer presence on drug and food intake. Although recording USV of rats self-administering drugs and palatable food as sucrose is common to assess the emotional status of the animals (Browning et al 2011; Barker, Simmons, & West 2015), no study has ever evaluated the effects of USV playback on drug and food intake, albeit other recent studies have shown that USV playback in rats is an essential tool to investigate different human brain disorders, especially those involving social communication deficits (Wöhr & Schwarting 2017). Moreover there are no studies regarding the neurobiological basis of the proximal social factor’s effects on drug and food consumption.…”